Cervical Spine Motion in the Elderly
Cervical Spine Motion in the Elderly
Rationale:

 Physiological motion of the cervical spine is a subject of interest for medical specialists.
 Segmental range of motion (sROM) has been most commonly used to define motion but inter- and
 intra-variability is large. Therefore, a sequence of segmental contributions in the lower
 cervical spine during the second half of extension has been defined in healthy participants
 (uniform in 80-90%). The mean age of these participants was 23 years. Since cervical
 degenerative disc disease (CDDD) occurs more often in elderly patients, it is of paramount
 importance to study whether this sequence remains present during aging, regardless of losing
 0.11 degrees of sROM each year.

 Objective:

 To investigate if the normal sequence of segmental contributions in the lower cervical spine
 during the second half of extension (C4-C5 followed by C5-C6, and then C6- C7) is also
 present in asymptomatic participants between 55 and 70 years of age by using cinematographic
 recordings.

 Study design:

 Fundamental research

 Study population:

 Eleven asymptomatic participants between 55 and 70 years of age, without a medical history of
 neck problems, with a score of 4 or less on the Neck Disability Index (NDI), and without
 severe degenerative changes based on a score of 3 or less on the radiological Kellgrens'
 classification.

 Intervention:

 Two flexion and extension cinematographic recordings of the cervical spine with a two-week
 interval between recordings.

 Main study parameters/endpoints:

 Primary endpoint: Defining the cervical spines' physiological motion pattern by analysing the
 normal sequence of segmental contributions in the lower cervical spine (C4-C5 followed by
 C5-C6, and then C6-C7) during the second halfof extension in asymptomatic participants
 between 55 and 70 years of age.

 Secondary endpoint: Determine sROM of C4-C5, C5-C6, and C6-C7 by analysing the flexion and
 extension cinematographic recordings in asymptomatic participants between 55 and 70 years of
 age.

 Nature and extent of the burden and risks associated with participation, benefit and group
 relatedness: Participants receive cinematographic recordings twice. There will be no
 follow-up.
INTRODUCTION AND RATIONALE Physiological motion of the cervical spine is a subject of
 interest for medical specialists. Although the term 'physiological motion' is commonly used,
 a proper definition has been lacking for a long time. Segmental range of motion (sROM, e.g.
 the amount of sagittal rotation in a segment between maximal flexion and maximal extension
 position of the entire cervical spine) is most commonly used to study motion. SROMs, however,
 suffer from large intra- and interindividual variability. Therefore, in the lower cervical
 spine, Boselie et al have recently described a consistent sequence of segmental contribution
 in sagittal rotation during flexion and extension in 20 healthy participants. This was based
 on historic reports. The mean age of the healthy participants was 23 years (SD 2.65, range
 18-55 years). They showed that the sequence of segmental contributions in the lower cervical
 spine during the second half of extension of the entire cervical spine and head was uniform
 in 80-90% of the healthy participants. The sequence of segmental contributions was C4-C5
 followed by C5-C6, and then C6-C7. Also, they described a group of single level cervical
 degenerative disc disease (CDDD) patients in which this sequence was present in only one
 patient (10%). This is the first method described which can reliably differentiate between
 normal or abnormal movement of the cervical spine in an individual subject. CDDD is
 degeneration of a cervical intervertebral disc and/or the adjoining vertebral bodies leading
 to cervical radiculopathy and/or myelopathy. CDDD occurs more often in elderly patients (> 50
 years of age) and due to aging of the population this will become a larger problem in the
 future. Age has been shown to be associated with a 0.11 degree decrease of sROM per year,
 independent of degeneration. Given that there are five levels in the subaxial cervical spine,
 there is an associated five degrees decrease in motion of the total subaxial cervical spine
 for every 10 years of ageing. It remains unclear whether the normal sequence of segmental
 contributions in the lower cervical spine is also present in asymptomatic elderly. By
 confirming the normal sequence in this group, this can be used to determine abnormal motion
 in elderly patients suffering from CDDD. The intention is to use this in future research in
 patients with cervical myelopathy or radiculopathy undergoing surgery to compare the outcomes
 of different types of surgery (e.g. cervical arthroplasty or anterior cervical discectomy
 with fusion) and to compare the influence of the type of surgery on normal motion.

 2. OBJECTIVES Primary Objective: To investigate whether the normal sequence of segmental
 contributions in the lower cervical spine during the second half of extension (C4-C5 followed
 by C5-C6, and then C6-C7), which is present in young asymptomatic controls, is similar in
 asymptomatic participants between 55 and 70 years of age by using cinematographic recordings.

 Secondary objective: To determine sROM of C4-C5, C5-C6, and C6-C7 by analysing the flexion
 and extension cinematographic recordings in asymptomatic participants between 55 and 70 years
 of age.

 3. STUDY DESIGN This is a fundamental research project in which asymptomatic elderly
 participants without neck pain or severe degenerative changes will be included. Participants
 will be recruited at Zuyd Hogeschool Sittard/Heerlen and Zuyderland Medical Center Sittard-
 Geleen/Heerlen by using posters notifying about the study. They can contact the researcher by
 email, who will inform them verbally and in writing. Informed consent will be signed if they
 meet the in- and exclusion criteria and if they are willing to participate. Flexion and
 extension of the cervical spine has been analysed through sagittal cinematographic recordings
 before. This was done in two groups with ten healthy participants in each group, from which
 an adequate analysis could be performed. Taking a possible loss to follow up of 10% into
 account, our study population will consist of 11 participants. No interim analysis will be
 performed. Each participant receives flexion and extension cinematographic recording twice to
 determine reproducibility and consistency of sequence between the two time points (T1 and
 T2). Recordings will be performed with an interval of two weeks, resulting in 22
 cinematographic recordings. Inclusion is expected to take approximately three months.
 Possible participants have to complete the Neck Disability Index (NDI), participants scoring
 above 4/50 points will be excluded (which means they would be no longer be classified as 'no
 disability due to neck problems'). A lateral X-ray of the cervical spine will be made, which
 will be scored using Kellgrens' classification by two neurosurgeons to avoid inclusion of
 participants with severe degenerative changes. Participants with a Kellgren score (KS) of
 four will be excluded. A KS score of four indicates severe degenerative changes such as
 severe narrowing of the disc space, severe sclerosis of the vertebral plates, or multiple
 large osteophytes. Participants with KS between zero and three will be included, indicating
 no, minimal, or moderate degenerative changes.

 4. STUDY POPULATION Population (base) Male and female participants between 55 and 70 years of
 age, without a history of neck complaints, an NDI score of 4 or less and a KS of 3 or less
 will be included. Participants will be recruited using posters in Zuyd Hogeschool
 Sittard/Heerlen and Zuyderland Medical Center Sittard- Geleen/Heerlen.

 Sample size calculation Sample size calculation is based on previous articles using the same
 method of cinematographic recordings to analyse motion of the cervical spine. Our study
 population will consist of 11 participants, assuming a possible loss to follow-up of 10%.
 Flexion and extension cinematographic recordings are acquired twice for each participant with
 an interval of two weeks in order to determine reproducibility and consistency of sequence of
 motion between two time points (T1 and T2). If there is no loss to follow-up and all
 cinematographic recordings are of good quality in the first 10 participants, the study will
 be ended.

 5. TREATMENT OF SUBJECTS 5.1 Investigational product/treatment Cinematographic recordings
 during flexion and extension of the cervical spine in asymptomatic elderly participants.

 5.2 Use of co-intervention Not applicable.

 5.3 Name and description of investigational product Not applicable.

 5.4 Summary of findings from non-clinical studies Not applicable.

 5.5 Summary of findings from clinical studies

 Initially, a method was developed to determine the ROM in the sagittal plane of the cervical
 spine using a fluoroscopy video of flexion-extension movement. The total ROM (tROM) and the
 sROM in 10 healthy participants (19-22 years) was investigated. The tROM for anteflexion is
 118.1 degrees and 114.3 degrees for retroflexion. Several new and very important insights
 have been published in this study. The maximum sROM is not necessarily reflected comparing
 the position of the vertebra in full flexion to its position in full extension. Moreover,
 sROM differs depending on execution of the motion from flexion to extension or the other way
 around and sROM can differ with time. A difference in excess of five degrees for the same
 segment in the same individual can be recorded. The cadence of movement in the cervical spine
 was also described. During flexion and extension, motion of the cervical vertebrae follows a
 general pattern which is complex and counter- intuitive. They conclude that tROM and sROM are
 unsuitable to be used as a parameter of cervical spine mobility.

 A review that systematically addressed contemporary knowledge about the mechanical behaviour
 of cervical vertebrae and soft-tissue of the cervical spine, under conditions that result in
 minor of major injuries. The results are collected from multiple studies that have measured
 sROM of individual joints of the cervical spine. It is emphasised that, even under normal
 conditions, sROM is not consistent either in time or according to the direction of motion.

 sROM and KS with flexion/ extension radiographs were assessed and the relation to clinical
 variables in 195 patients was determined (age 15-93 years, 62 males and 133 females).
 Interobserver reliabilities for assessing KS (intraclass correlation coefficient 0.81) and
 sROM (intraclass correlation coefficient 0.72) were good to excellent. Age had a significant
 negative association with sROM at C2-C3, C3-C4, C4-C5, and C5-C6, amounting to a total of
 five degrees decrease in subaxial cervical ROM every 10 years. KS at the level of interest
 had a significant negative association with sROM at C2-C3, C3-C4, C4- C5, C5-C6, and C6-C7.
 KS at the inferior segment had a significant positive association with sROM at C2-C3, C3-C4,
 and C4-C5. For every point increase in KS at a given level, there was an associated 1.2
 degrees decrease in sROM at that level, and 0.8 degrees increase in sROM at the level above.
 Gender had a significant association with sROM only at C2-C3.

 A non-invasive infrared system Polaris was used to quantify the 3D tROM of the cervical spine
 in 140 asymptomatic volunteers (age 20-93 years, 70 males and 70 females). The standard error
 of measurement for the maximum tROM in 3D space planes was 5%. Gender had no significant
 influence on the 3D cervical tROM. Age had a significant influence on all main movements
 showing 0.55 - 0.79 degrees magnitude decrease per decade per segment.

 Later, an automatic fast and precise method for tracking cervical vertebrae in fluoroscopy
 videos of flexion- extension movement of the cervical spine was developed. The method relies
 only on a rough selection of template areas of each vertebra in a single frame of the video
 sequence, no contours need to be extracted and no vertebra segmentation is required. Tracking
 is done with a normalized gradient field, using only the gradient orientations as features.
 Results show that the algorithm is robust and able to track the vertebrae accurately, even if
 they are partially occluded or if a disc prosthesis is present.

 A clear definition of the normal sequence of segmental contributions in the cervical spine
 using extension cinematographic recordings (ECRs) was defined. They analysed healthy
 participants (n=20) and patients with CDDD (n=10). ECRs were more consistent than flexion
 cinematographic recordings (FCRs) and were therefore used to define "normal" motion. A
 consistent sequence of contribution of sagittal rotation of the three lower cervical motion
 segments C4-C7 was especially identified in the last phase of extension in healthy
 participants. The first peak was found for C4- C5, followed by C5-C6 and finally in C6- C7.
 Sensitivity, specificity, and reliability were calculated. Reliability of scoring as normal
 or abnormal is high (Fleiss kappa of 0.80-0.84, range of 95% CI: 0.66- 0.98). Sensitivity and
 specificity are also high, with an average sensitivity of 90% (range of 95% CI: 78.4 -
 99.8%), nd an average specificity of 85% (range of 95% CI: 72.9 - 96.4%). This is the first
 described method which can reliably differentiate between normal or abnormal movement of the
 cervical spine in an individual subject.5.6 Summary of known and potential risks and benefits
 Flexion- and extension cinematographic recordings are made using the Philips Allura Xper FD20
 X-ray system. Radiation dose per cinematographic recording, determined by radiation experts,
 will be around 0.084 mSv. Participants will perform cinematographic recordings twice,
 resulting in a total radiation dose of 0.168 mSv. Moreover, before definitive inclusion in
 the study a lateral X-ray of the cervical spine will be performed to determine eligibility
 resulting in a radiation dose of 0.0096 mSv. Average radiation dose per participant will
 therefore be 0.1776 mSv. This amount of radiation can be categorized in category IIa using
 the Neurocritical Care Society (NCS) guidelines about risks of radiation dosage (0.1 to 1
 mSv) 11. This category includes moderate risk which can be justified if there is a potential
 health benefit for future patients.

 6. METHODS 6.1 Study parameters/endpoints

 6.1.1 Main study parameter/endpoint To investigate whether the normal sequence of segmental
 contributions in the lower cervical spine during the second half of extension (C4-C5 followed
 by C5-C6, and then C6-C7), which is present in young asymptomatic controls, is similar in
 asymptomatic participants between 55 and 70 years of age by using cinematographic recordings.
 Recordings will be made at two occasions, with an interval of two weeks. These will then be
 analysed within one year.

 6.1.2 Secondary study parameters/endpoints (if applicable) Analysing sROM of C4-C5, C5-C6 and
 C6-C7 by analysing the flexion and extension cinematographic recordings in asymptomatic
 participants between 55 and 70 years of age. Recordings will be made at two occasions, with
 an interval of two weeks. These will then be analysed within one year.

 6.2 Randomisation, blinding and treatment allocation Not applicable.

 6.3 Study procedures This study does not use invasive procedures, but is not regular care.

 Investigations before inclusion in the study:

 Lateral X-ray of the cervical spine to determine Kellgrens' classification. The KS will be
 determined by two neurosurgeons and is a scoring method to determine severity of degenerative
 disc disease, using five gradations :

 Grade 0: absence of degeneration in the disc. Grade 1: minimal anterior osteophytosis. Grade
 2: definite anterior osteophytosis, possible narrowing of the disc space, some sclerosis of
 the vertebral plates.

 Grade 3: moderate narrowing of the disc space, sclerosis of the vertebral plates,
 osteophytosis.

 Grade 4: severe narrowing of the disc space, severe sclerosis of the vertebral plates,
 multiple large osteophytes.

 Questionnaire the NDI:

 The NDI is a modification of the Oswestry Low Back Pain Disability Index. It is a patient-
 completed, condition-specific functional status questionnaire with 10 items including pain,
 personal care, lifting, reading, headaches, concentration, work, driving, sleeping and
 recreation. Each section is scored on a 0 to 5 rating scale, in which zero means 'No pain'
 and 5 means 'Worst imaginable pain'. Al the points can be summed to a total score. The test
 can be interpreted as a raw score, with a maximum score of 50, or as a percentage. 0 points
 or 0% means: no activity limitations, 50 points or 100% means complete activity limitation.

 Investigations during the study:

 - Cinematographic recordings: participants are seated on a crutch, adjustable in height, with
 their neck, shoulders and head free. Before recordings are made, participants will be taught
 to perform the prescribed flexion and extension movement on about 16 seconds using a
 metronome. Participants are placed on the crutch with their shoulder's perpendicular to the
 image intensifier to obtain sagittal images from the occiput till C7. As soon as the
 recording is started, the participant is instructed to move his head in the sagittal plane
 from maximal ex- tension to maximal flexion, without moving the upper part of the body. It is
 important that the participants shoulders are kept as low as possible while making the
 recordings to ensure that all the cervical vertebrae are visible. The movement of the
 cervical spine should be as fluent as possible to prevent for sudden large rotations and
 translations between consecutive frames. The cinematographic recordings will be made twice
 with an interval of two weeks using the Philips Alura Xper FD20 X- ray system. To stay below
 the limit of 1 mSv per participant, the 0.9 mm Cu + 1 mm Al filter will be used for the
 entire study. The Alura Xper automatically selects correct tube voltage, with an expected
 maximum around 70-80 kV for cervical cinematographic recordings.

 6.4 Withdrawal of individual subjects Participants can cease study participation at any time
 for any reason if they wish to do so, without any consequences. If participants leave the
 study before the second recording, only the first recording will be included and analysed.

 Researchers cannot decide to withdraw participants from the study, unless participants do not
 respond to calls before the first cinematographic recording is made.

 6.5 Replacement of individual subjects after withdrawal If a participant withdraws before the
 first cinematographic recording is made, researchers are allowed to replace this
 participant.cal cinematographic recordings.

 6.6 Follow-up of subjects withdrawn from treatment Participants who withdraw from the study
 will not be actively recalled.

 6.7 Premature termination of the study Interim analysis will not be performed, so there will
 be no reason to terminate the study prematurely.

 7. SAFETY REPORTING 7.1 Temporary halt for reasons of subject safety In accordance to section
 10, subsection 4, of the WMO, the investigator will suspend the study if there is sufficient
 ground that continuation of the study will jeopardise subject health or safety. The sponsor
 will notify the accredited METC without undue delay of a temporary halt including the reason
 for such an action. The study will be suspended pending a further positive decision by the
 accredited METC. The investigator will take care that all subjects are kept informed.

 7.2 AEs, SAEs and SUSARs 7.2.1 Adverse events (AEs) Adverse events are defined as any
 undesirable experience occurring to a participant during the study, whether or not considered
 related to experimental intervention. All adverse events reported spontaneously by the
 participant or observed by the investigator or his staff will be recorded.

 7.2.2 Serious adverse events (SAEs) A serious adverse event is any untoward medical
 occurrence or effect that results in: Death.

 Is life threatening (at the time of event). Requires hospitalization or prolongation of
 existing inpatients' hospitalization. Results in persistent or significant disability or
 incapacity.

 Is a congenital anomaly or birth defect. Any other important medical event that did not
 result in any of the outcomes listed above due to medical or surgical intervention but could
 have been based upon appropriate judgement by the investigator. An elective hospital
 admission will not be considered as a serious adverse event. The investigator will report all
 SAEs to the sponsor without undue delay of obtaining knowledge of the events. Sponsor will
 report these SAEs through the web portal ToetsingOnline to the accredited METC that approved
 the protocol, within 7 days for SAEs that result in death or life- threatening event,
 followed by a period of maximum of 8 days to complete the initial preliminary report. All
 other SAEs will be reported within a period of maximum 15 days after sponsor has first
 knowledge of the serious adverse events.

 7.3 Follow-up of adverse events All AEs will be followed until they have abated, or until a
 stable situation has been reached. Depending on event, follow up may require additional tests
 or medical procedures as indicated, and/or referral to general physician or medical
 specialist. SAEs need to be reported till end of study (last follow up moment for last
 subject), as defined in the protocol.

 8. STATISTICAL ANALYSIS 8.1 Primary study parameter(s) The primary study parameter is to
 define if the normal sequence of segmental contributions in the lower cervical spine during
 the second half of extension (C4-C5 followed by C5-C6, and then C6-C7) is present in
 asymptomatic participants between 55 and 70 years of age by using cinematographic recordings.
 Participants are seated on a crutch, adjustable in height, with their neck, shoulders and
 head free. As soon as the recording is started, the participant is instructed to move his
 head in the sagittal plane from maximal extension to maximal flexion, without moving the
 upper part of the body, in about 16 seconds. Participants perform this procedure twice with
 an interval of two weeks. Images will be analysed using computer software that uses an
 algorithm to follow motion of the vertebrae during complete flexion and extension. This will
 be done by two researchers for 4 cinematographic recordings to determine reproducibility
 using two way mixed, absolute agreement, intra-class correlation coefficient. Graphs will be
 made for flexion and extension in which segmental rotation between each pair of successive
 frames of each individual segment within C4 to C7 will be plotted against the cumulative
 rotation in segments C4 to C7 together (block C4-C7) to describe the sequence of segmental
 contributions during flexion and extension. These graphs will be made and analysed for each
 individual participant to determine if the normal sequence of segmental contributions is
 present or absent. T1 will be tested against T2 using coefficient of variation and
 intra-individual standard deviation to determine if the defined sequence is consistent
 between two recordings in the intra-individual variability.

 8.2 Secondary study parameter(s) The secondary study parameter is defining the sROM of C4-C5,
 C5-C6 and C6- C7 by analysing the flexion and extension cinematographic recordings in
 asymptomatic participants between 55 and 70 years of age. Rotation within a segment is
 calculated between each pair of successive frames to be able to determine the sequence of
 segmental contributions. All these small rotations from extension to flexion (or vice versa)
 can be summated to calculate sROM for that motion segment.

 9. ETHICAL CONSIDERATIONS 9.1 Regulation statement This research is conducted according to
 principles enshrined in the Declaration of Helsinki (3th edition 2013) and in accordance with
 the Medical Research Involving Human Subjects Act (WMO, version 1 July 2012).

 9.2 Recruitment and consent Participants will be recruited from Zuyd Hogeschool
 Sittard/Heerlen and Zuyderland Medical Center Sittard-Geleen/Heerlen using posters. Possible
 participants have to contact the researcher by email if they are interested in participation.
 Further information will be given verbally and in writing, followed by a thinking time of
 seven days. When people are willing to participate and meet the inclusion criteria, informed
 consent will be signed during the first meeting between researcher and participant.
 Participants can terminate their participation at all times, without giving a reason. For any
 questions regarding the study, an independent physician is available throughout the duration
 of the study.

 9.3 Objection by minors or incapacitated subjects (if applicable) Not applicable.

 9.4 Benefits and risks assessment, group relatedness Participants do not directly benefit
 from participating in this study. They make a contribution to knowledge in the field of
 motion of the cervical spine in the elderly population. Increased knowledge of physiological
 motion enables us to recognize abnormal motion in future. Phantom measurements of the Alura
 Xper in Zuyderland Sittard were used to determine radiation dosage. According to radiation
 experts, radiation dosage per cinematographic recording will be 0.084 mSv. Participants will
 perform cinematographic recordings twice, resulting in a total radiation dose of 0.168 mSv.
 Moreover, before definitive inclusion in the study a lateral X-ray of the cervical spine will
 be performed to determine eligibility resulting in a radiation dose of 0.0096 mSv. Total
 radiation dose per participant will therefore be 0.1776 mSv. This amount of radiation can be
 categorized in category IIa using the NCS guidelines about risks of radiation dosage (0.1 to
 1 mSv). This category includes moderate risk which can be justified if there is a potential
 health benefit for future patients.

 9.5 Compensation for injury The sponsor/investigator has a liability insurance which is in
 accordance with article 7 of the WMO. The sponsor (also) has an insurance which is in
 accordance with the legal requirements in the Netherlands (Article 7 WMO). This insurance
 provides cover for damage to re- search subjects through injury or death caused by the study.
 The insurance applies to the damage that becomes apparent during the study or within 4 years
 after the end of the study.

 9.6 Incentives (if applicable) Participants will be reimbursed for extra time that is needed
 to fill out the questionnaires and undergo cinematographic recordings. They will receive €50
 for participating in T1 and T2. Participants that live outside of Sittard will receive
 mission expenses of €0.20 per kilometre.

 10. ADMINISTRATIVE ASPECTS, MONITORING AND PUBLICATION 10.1 Handling and storage of data and
 documents Data will be stored in two ways; cinematographic recordings on CDs and
 questionnaires on paper. Both of them will be coded with participant-number (e.g. participant
 5). Cinematographic recordings will also be coded with recording-number (e.g. recording 5).
 CDs and questionnaires will be locked up in a secured room in the Maastricht University
 Medical Centre (MUMC+). Data analysis will also take place in the MUMC+. Data will be kept
 for 15 years after ending the study. Handling of personal data will comply with the Dutch
 Personal Data Protection Act (Wbp).

 10.2 Monitoring and Quality Assurance Monitoring will be performed by trained and qualified
 monitors. According to Good Clinical Practice (GCP) guidelines main task of the monitor is
 ensuring that: Rights and well-being of human participants are protected.

 Reported trial data are accurate, complete and verifiable from source documents.

 Conduct of trial is in compliance with currently approved protocol, GCP and applicable
 regulatory requirements.

 Prior to the study start a monitoring plan will be assembled, specifying Source Document
 Verification Plan, frequency of monitoring visits and frequency of checking Trial Master
 Files/Investigator Site Files.

 Monitoring will be performed remotely and on site.

 There are several kinds of monitoring visits:

 Site initiation visit (SIV): SIV will be performed after all approvals have been obtained and
 prior to enrolling the first subject in that centre.

 Interim monitoring visit (IMV): Several IMV's will be performed during the trial.

 Frequency of visits is determined in monitoring plan.

 - Close out visit (COV): COV will be performed at the end of the trial, after collection of
 all data. Monitoring visits will be planned in agreement with study site personnel. According
 to GCP guidelines, the investigators must provide the monitor with all necessary information
 and documents. Furthermore, the investigators are obliged to answer all queries raised by
 monitor in eCRF in timely manner. After each monitoring visit, a follow-up email with all
 action points will be sent to the study site. These action points will be addressed at
 beginning of the next monitoring visit.

 10.3 Amendments Amendments are changes made to the research after a favourable opinion by the
 accredited METC has been given. All amendments will be notified to the METC that gave a
 favourable opinion.

 10.4 Annual progress report The researcher will submit a summary of progress of the trial to
 the accredited METC once a year. Information will be provided on date of inclusion of the
 first subject, numbers of subjects included and numbers of subjects that have completed the
 trial, serious adverse events, other problems, and amendments.

 10.5 Temporary halt and (prematurely) end of study report The researcher will notify the
 accredited METC of the end of the study within a period of 8 weeks. The end of the study is
 defined as the last participants' last visit. The researcher will notify METC immediately of
 a temporary halt of the study, including reason of such an action. In case of ending the
 study prematurely, the researcher will notify the accredited METC within 10 days, including
 reasons for premature termination. Within one year after the end of the study, the researcher
 will submit a final study report with results, including any publications/abstracts, to the
 accredited METC.

 10.6 Public disclosure and publication policy This trial will be registered in a public trial
 register before recruitment of the first participant. Results will preferable be published in
 open access, peer-reviewed journals. Data of participants will be anonymous for publication
 and cannot be traced to an individual. In case of negative results, data will also be
 published. Possible funding has through contractual agreement no effect on publication. There
 is no veto over whether or not to publish data by one of the parties.
Inclusion Criteria:

 1. Age 55-70 years.

 2. Ability to actively perform flexion/extension movements of the neck without pain or
 other symptoms.

 3. No history of neck complaints.

 4. Neck Disability Index (NDI) score of 4 or less.

 5. Kellgren's score of 3 or less.

 6. Informed consent

 Exclusion Criteria:

 1. Previous surgery on the cervical spine.

 2. Symptoms of cervical radiculopathy of myelopathy (e.g. positive Lhermitte's sign).

 3. Active infection.

 4. Immature bone.

 5. Previous or actual tumorous processes in the cervical region.

 6. Previous radiation therapy in the cervical region.

 7. Not able to speak Dutch.