The Effect of a Complementary Multi Disciplinary Program on Blood Pressure in Hypertensive Patients
The Effect of a Complementary Multi Disciplinary Program on Blood Pressure in Hypertensive Patients
Intervention description:

 Complementary Approaches to Lower Mean arterial pressure (CALM) is a multi dispensary program
 aimed to reduce blood pressure in hypertensive patients. The program utilizes a naturopathic
 dietary approach, education on cooking and food consumption choices, walking physical
 exercise, Qi Gong - a form of Chinese slow movement exercise combined with relaxation
 breathing and imagery and group therapy coaching in stress management techniques and
 mind-body balancing techniques.

 Trial Objectives:

 To compare the effect of CALM in reducing blood pressure to the standard dietary DASH
 approach in hypertensive patients.

 Methodology:

 120 Participants will be randomly assigned in to two groups:

 -  CALM program for reducing blood pressure as the treatment group.

 -  Standard DASH diet and lifestyle modification counseling as the control group. Inclusion
 Criteria

 -  Adult men and women over 18 years.

 -  Patients using anti hypertensive medications with mean systolic blood pressure
 measurements of 120-180 mm Hg and/or mean diastolic measurements of 70-100 mm Hg as
 determined by a 24 hour Holter test.

 -  Patients not using anti hypertensive medications with mean systolic blood pressure
 measurements of 130-180 mm Hg and or mean diastolic measurements of 80-100 mmHg.

 -  Signed informed consent (appears in IRB forms)

 Assessment of Efficacy Primary end point efficacy will be assessed by comparing the mean BP
 measurements in the CALM group to the mean BP measurements in the DASH control group. Blood
 pressure measurements will be performed by 24 hours Holter BP monitoring in the beginning and
 at the end of the trial.

 Secondary end points efficacy will be assed by comparing CALM to DASH programs with respect
 to effects use of BP medications and weight loss. Lab test and pulse wave analysis will also
 be assessed at the beginning and at the end of the study.
Intervention description Complementary Approaches to Lower Mean arterial pressure (CALM)
 utilizes a naturopathic dietary approach, education on cooking and food consumption choices,
 walking physical exercise, Qi Gong - a form of Chinese slow movement exercise combined with
 relaxation breathing and imagery and group therapy coaching in stress management techniques
 and mind-body balancing techniques.

 Trial Objectives

 Primary objective To compare the effect of CALM in reducing blood pressure to the standard
 dietary DASH approach in hypertensive patients.

 Secondary objectives To provide information on the efficacy of CALM in reducing weight and
 improving quality of life. and to examine it's potential to indicate a dose reduction in
 hypertensive medications. To evaluate CALM effects on cardiovascular disease risk factors.

 Trial Design

 A single center parallel randomized control trial including two groups and enrolling 120
 participants.

 Primary End Point A comparable change in blood pressure measurements between CALM and DASH
 groups after the 16 week period of the trial as measured by a 24 hour holter test which will
 be performed in the beginning and the end of the study.

 Secondary End Points

 A comparable change in hypertensive medications A comparable change in weight reduction

 Comparable changes in cardiovascular risk factors as indicated by following laboratory tests
 and evaluations :

 Arterial wall thickening , hemoglobin, hemoglobin A1c, creatinine, liver function parameters,
 highly sensitive c-reactive protein (hsCRP), low density lipoprotein (LDL), high density
 lipoprotein (HDL), triglycerides (TG), oxidized LDL (oxLDL), nitric oxide metabolites and
 microalbumine/creatinine ratio.

 Methodology 120 Participants will be randomly assigned in to two groups:

 -  CALM program for reducing blood pressure as the treatment group.(As described below in
 section 6)

 -  Standard DASH diet and lifestyle modification counseling as the control group. (As
 described below in section 6)

 Duration of the study Group intervention in the treatment arm consists of 16 weeks of the
 CALM program. Due to the limited number of participants we can allocate to each group, three
 16 weeks cycles will be repeated in order to recruit the needed number of participants for
 the trial. Thus the treatment phase is expected to last for 48 weeks. Recruitment is expected
 to last about three months. An additional 6 months will be required for completion of data
 entry and analysis.

 Location of the study The study will take place in Asaf Harofeh Medical Center, Israel and
 will be conducted in Shiram - The Department of Integrated Medicine and in the Research and
 Development Unit of Assaf Harofeh Medical Center.

 Recruitment of the Subjects Patients will be recruited from the community and from Asaf
 Harofeh medical center. Patients from a number of departments within the hospital will be
 invited to participate in the study. An advertisement in the local newspaper and in the
 medical center's web site will be published (appears in IRB forms) Recruitment will continue
 until the overall quota of subjects (50 per group) will be met.

 Randomization Subjects will be randomly assigned to each treatment group utilizing a
 computerized randomization system. A random list will be generated by the study statistician.
 The random list will be kept in a sealed envelope in the study site. The list will be readily
 available in case of any emergency.

 Follow up Subjects will be assessed in the beginning and at the end of the trial and again 6
 months later. Compliance questioners will be filled during several stages of the trial as
 described in section 8 below.

 Study Population Inclusion Criteria

 -  Adult men and women over 18 years.

 -  Patients using anti hypertensive medications with mean systolic blood pressure
 measurements of 120-180 mm Hg and/or mean diastolic measurements of 70-100 mm Hg as
 determined by a 24 hour Holter test.

 -  Patients not using anti hypertensive medications with mean systolic blood pressure
 measurements of 130-180 mm Hg and or mean diastolic measurements of 80-100 mmHg.

 -  Signed informed consent Exclusion Criteria

 -  Cardiovascular event within the past 6 months

 -  Inability to walk independently for 15 or less minutes.

 -  Poorly controlled insulin dependant diabetes mellitus with Hg A1c measurements over 7.5.

 -  Inflammatory bowl disorders

 -  Acute malignancy with life expectancy of less than 5 years.

 -  Pregnancy or lactation

 -  A body mass index of more than 35.

 -  More than 20 alcoholic beverages per weak.

 -  Change in anti hypertensive medications within the last 3 months.

 -  Planning to change smoking habits

 Treatment of the subjects

 The CALM group will receive a weekly 4 hour group coaching session for 16 weeks. Each session
 will include the following parts:

 1. A group aerobic walking session. Participants will reach a target heart rate which will
 be determined in advance as 60-75% of maximal heart rate expected for their age and with
 accordance to their physical ability. The group walk will last for a maximum of one
 hour. All participants will be encouraged to walk at least 3 times per week
 independently.

 .

 2. A 1 hour weekly Qi Gong session. The class will include 45 minutes of slow movement
 exercises emphasizing relaxation, abdominal breathing and visualization stretching and
 meditation. A 15 minutes prerecorded guided imagery meditation aimed to reduce blood
 pressure will be performed in a seated or supine position. Participants will be given a
 CD with the 15 minutes mediation and will be encouraged to use it at home once a day.

 3. Dietary counseling and cooking instructions for forming a healthy home cooking routine
 which will be based on naturopathic rice diet approach. A group meal will be prepared by
 participants in each session and participants will dine together. All participants will
 be encouraged to follow the same diet at home.

 4. Group therapy meeting focusing on stress management techniques and mind - body
 balancing. Emphasis will be put on developing communication skills based on
 nonjudgmental and empathic approaches, methods for dealing with stress and anxiety,
 discarding low self esteem and negative thought patterns and developing positive
 thinking patterns.

 The DASH control group will receive group coaching sessions for 16 weeks. Each session will
 include the following parts:

 1. A group aerobic walking session. Participants will reach a target heart rate which will
 be calculated in advance as 60-75% of maximal heart rate expected for their age. The
 group walk will last for a maximum of one hour. All participants will be encouraged to
 walk at least 3 times per week independently.

 2. Dietary counseling and cooking instructions according to a standard DASH diet. This will
 include a diet rich in fruits, vegetables and low fat dairy products. A group meal will
 be prepared by participants in each session and participants will dine together. All the
 participant will be encouraged to follow the same diet at home.

 Assessment of Efficacy

 Primary end point efficacy will be assessed by comparing the mean BP measurements in the CALM
 group to the mean BP measurements in the DASH control group. Blood pressure measurements will
 be performed by 24 hours Holter BP monitoring in the beginning and at the end of the trial.

 Secondary end points efficacy will be assed by comparing CALM to DASH programs with respect
 to effects use of BP medications and weight loss. Lab test and pulse wave analysis will also
 be assessed at the beginning and at the end of the study.

 Pulse wave analysis Assessment of arterial stiffness will be performed, at baseline, at the
 end of 16 weeks of the trial and following 6 months, by a noninvasive technique using the
 commercially available SphygmoCor System (AtCor Medical,LTD, Australia). All measurements
 will be performed by S.E while the patient is in the recombinant position at room temperature
 of 25oc. In brief, peripheral pressure waveforms will be recorded from the radial artery at
 the wrist, using applanation tonometry with a high-fidelity micromanometer (Millar
 Instruments). When 20 sequential waveforms will be recorded, a validated 16-18 generalized
 transfer function will be applied to generate the corresponding central aortic pressure
 waveform. Augmentation index (AIx) and augmented pressure (AP) were derived by calculation,
 using pulse wave analysis technique. The merging point of the incident and the reflected wave
 (the inflection point) will be identified on the generated aortic pressure waveform. AP will
 be calculated as maximum systolic pressure minus pressure at the inflection point. AIx will
 be calculated as AP divided by pulse pressure and expressed as percentage. Higher values of
 AIx indicated increased wave reflection from the periphery or earlier return of the reflected
 wave as a result of increased pulse wave velocity (attributable to increased arterial
 stiffness), and vice versa. Only high-quality recordings, defined as those with in-device
 quality index >80% (as derived from an algorithm including average pulse height, pulse height
 variations, diastolic variations, and the maximum rate of rise of the peripheral waveform)
 and the curves acceptable upon a visual inspection performed by one investigator, will be
 included in the analysis. All pulse wave measurements will be taken in the same sitting
 position, in a quiet, temperature controlled room (23 ± 1°C), after at least 15 minute
 resting period.

 Laboratory Tests At the beginning and at the end of the study, blood will be drawn for
 measurement of hemoglobin, hemoglobin A1c, creatinine, liver function tests, highly sensitive
 c-reactive protein (hsCRP) and lipid profile including total cholesterol high density
 lipoprotein (HDL) and triglycerides (TG). LDL will calculated. Five cc of plasma will be
 preserved in -70oc for future evaluation of oxidative stress (oxLDL, MDA) and NO.

 Life Quality & well being questioners Patients will fill the MOS 36 life quality
 questionnaire in the beginning, at week 4, week 10 and at the end of the trial. In addition a
 specific questionnaire for assessing dietary and cooking lifestyle will be filled in the
 begging and at the end of the trial. These questionnaires will again be after six months for
 the follow up period.

 Compliance Compliance questionnaires will address three topics: adherence to the diet
 recommendations and cooking instructions at home, number of exercise sessions per week and
 frequency of using the Qi Gong meditation disk at home. Questionnaires will be filled at the
 end of weeks 4,10 & 16 (end of trial) and at the follow up meeting post 6 months.

 Assessment of Safety No adverse events or risks are expected for participants enrolled in
 this trial. However, initially, the strict dietary program may influence the participants
 overall energy level. Transient symptoms such as dizziness and headaches may also present in
 early stages of the study participants will be couched in advance on how to maintain any
 undesired influences. Nevertheless, any adverse event will be reported on the Adverse Event
 Form along with the probability of the adverse event being study-related.

 Decreasing doses or cessation of BP Medications use BP medication doses will be changed by
 the primary investigator or by the patient healthcare physician. The physician in charge will
 reduce BP lowering medications in case systolic blood pressure will decrease below 110 mmHg
 or if participants will present symptoms of low blood pressure such as weakness, ortostatizm,
 dizziness, presyncope or syncope. Before any change in BP lowering medications patients will
 be encouraged to get another 24 hours holter of BP measurement test. All changes in BP
 medications will be recorded.
Inclusion Criteria:

 -  Adult men and women over 18 years.

 -  Patients using anti hypertensive medications with mean systolic blood pressure
 measurements of 120-180 mm Hg and/or mean diastolic measurements of 70-100 mm Hg as
 determined by a 24 hour Holter test.

 -  Patients not using anti hypertensive medications with mean systolic blood pressure
 measurements of 130-180 mm Hg and or mean diastolic measurements of 80-100 mmHg.

 -  Signed informed consent

 Exclusion Criteria:

 -  Cardiovascular event within the past 6 months

 -  Inability to walk independently for 15 or less minutes.

 -  Poorly controlled insulin dependant diabetes mellitus with Hg A1c measurements over
 7.5.

 -  Inflammatory bowl disorders

 -  Acute malignancy with life expectancy of less than 5 years.

 -  Pregnancy or lactation

 -  A body mass index of more than 35.

 -  More than 20 alcoholic beverages per weak.

 -  Change in anti hypertensive medications within the last 3 months.

 -  Planning to change smoking habits