Efficacy and Safety of a Nutraceutical Supplement With Standardized Botanicals in Women With Thinning Hair
Efficacy and Safety of a Nutraceutical Supplement With Standardized Botanicals in Women With Thinning Hair
NUTRAFOL® is a novel nutraceutical supplement, scientifically formulated to specifically
 target the multiple underlying causes of hair loss and thinning in women. It does not contain
 hormones, drugs, or industry by-products.

 The purpose of this clinical research study is to evaluate the safety, efficacy and
 physiological effects of NUTRAFOL® supplement compared to placebo in forty (40) female
 subjects, ages 21-65 years of age with self-perceived thinning hair over the course of six
 months of continued use.
NUTRAFOL's Synergen Complex® is a patent-pending formulation of botanicals with potent
 anti-inflammatory, anti-stress adaptogenic, antioxidant and DHT-inhibiting properties -
 combined to synergistically combat the multiple underlying factors that compromise hair
 growth and health. Some patented ingredients include Sensoril Ashwagandha, BCM-95
 BioCurcumin, USPlus Saw Palmetto, EVNolMax 20% Tocotrienol/Tocopherol complex, Bioperine
 (piperine), Cynatine HNS (solubilized keratin), and Capsimax (capsaicin), all of which are
 standardized and clinically tested.

 Ingestion of NUTRAFOL® supplement over a six (6) month period will strengthen and promote the
 growth of hairs in female subjects, ages 21-65 years of age with self-perceived thinning hair
 when compared to using the placebo tablet. The primary endpoints will be favorable analysis
 using the Canon Power Shot G16 with 3GEN Dermlite FOTO Pro for macrophotography hair count
 analysis of terminal and vellus hairs at the three (3) month and six (6) month visits. The
 secondary endpoints will be favorable improvement in terminal hair diameter measured by the
 Dino-Lite Digital Microscopic, favorable improvement in the Hair Check device hair bundle
 measurement for Hair Mass Index (HMI), favorable improvement in the Blinded Physician Global
 Hair Assessments for hair growth and hair quality, statistically significant positive
 feedback on the Women's Hair Loss Quality of Life, Self-Assessment and Subject Treatment
 Satisfaction and Ease of Use questionnaires after six (6) months of NUTRAFOL® supplement or
 placebo ingestion. See Table of Study Procedures.

 All patients enrolled must be identifiable throughout the study. The Investigator will
 maintain a personal list of patient numbers and patient names to enable records to be found
 at a later date and the list will be stored in a locked cabinet. Subject numbers consist of a
 2 digit number from 01 to 40. Patients will be randomized to active or placebo supplements
 (2:1 ratio, 26 active and 14 placebo) using a randomization table prepared prior to the start
 of the study by a non-participating staff member at the office of the Investigator. The study
 blind will not be broken until the end of the study. All test product and placebo will be
 labeled with subject numbers per the non-participating staff member. Subjects will be
 assigned a subject number in numerical order as enrolled. Randomization will occur by
 assignment to either NUTRAFOL® supplement or placebo with 2:1 ratio (26 active and 14
 placebo). Subjects who terminate their study participation for any reason, regardless of
 whether study medication was used or not, will retain their randomization number.

 Visit Procedures: Pre-Study Procedures

 1. Candidate subjects will be screened with the eligibility requirements by telephone prior
 to Visit 1.

 2. Candidate subjects will be assigned an appointment time for visiting the clinic.

 Visit 1: Baseline, Day 0

 1. Individuals will be given an informed consent (IC) document & photographic release form,
 HIPAA form, confidentiality agreement to read. They will have all of their study related
 questions answered by the Investigator or his/her designated staff and if they agree,
 they will sign two copies of the IC/Photography release form, two copies of the HIPAA
 form, and one copy of the confidentiality agreement. Subjects will be given one copy of
 the signed IC/Photography release and of the HIPAA agreement to keep, with one copy of
 each document remaining at the testing facility in the subject's file.

 2. Investigator and/or Study Coordinator will review with subject and complete the
 checklist for all inclusion and exclusion criteria.

 3. Investigator and/or Study Coordinator will review with subject and complete the
 checklist for medical history and concomitant medications.

 4. Investigator and/or Study Coordinator will review with subject and complete the General
 Lifestyle Questionnaire. The General Lifestyle Questionnaire may be found in Appendix
 VI.

 5. Subjects will be given a Women's Hair Loss Quality of Life Questionnaire to read and
 complete. The Quality of Life Questionnaire may be found in Appendix VII.

 6. Candidate subjects will receive a brief physical exam, including examination of the
 scalp, to rule out any immediately observable medical issues and any scalp
 alopecias/scalp disorders that are unacceptable for qualification. The physical will
 additionally include vital signs (pulse and blood pressure), weight and height.

 7. Candidate subjects of childbearing potential will complete a urine pregnancy test prior
 to product distribution.

 8. Candidate subjects who have completed all the initial paperwork and meet the
 inclusion/exclusion qualifications (to include findings of the physical exam) will be
 assigned a unique subject number. Subjects will be randomized to treatment group prior
 to dispensing the test product.

 9. Qualified subjects will have 2D digital photography of the entire head/hair region for
 overall general hair growth and fullness (see Appendix I).

 10. Qualified subjects will have their scalp prepared for digital macrophotography and
 initial target area measurements done (see Appendix II).

 11. Subjects will have the selected target area (1cm x 1cm) photographed (see Appendix II).

 12. Subjects will have the extended target area (2cm x 2cm) bundle of hair measured for Hair
 Mass Index (HMI) (see Appendix III).

 13. Subjects will have ten (10) terminal hairs in a selected test site cut at the base of
 the scalp and the diameter of the hairs measured (see Appendix IV).

 14. Subjects will be dispensed a three (3) month supply of the test product (NUTRAFOL®
 supplement or Placebo, as randomized) and given written and verbal Usage and Lifestyle
 instructions (see Appendix X) and a calendar of future visits. Subjects will be
 instructed to ingest the test product per Sponsor instructions.

 Usage Instructions:

 Take 4 capsules once daily, along with a meal or immediately following (within 5 minuntes) at
 approximately the same time of the day, every day. Do not take on an empty stomach. If you
 forgot to take your dose during a meal, do not skip the dose, take it with something fatty,
 like peanut butter or coconut oil when you remember. Store at room temperature, in a cool dry
 location. Do not take if broken or seal is compromised.

 Subjects will be instructed to return all empty bottles and unused test product at Visits 2
 and 3.

 Lifestyle Instructions:

 Subjects will be instructed to maintain their normal hair care routine. Subjects will be
 instructed to use the same brand/type of hair care products and maintain the same haircut,
 color and style for the study duration.

 Subjects who have color treated hair will also be instructed to have the color treatment
 performed at the same time interval prior to each visit (ie. If on Visit 1, the color
 treatment was done one week prior then the color treatment is expected to occur at a similar
 interval of one week prior to Visits 2 and 3).

 Subjects will be instructed to come to each visit with clean and dry hair.

 Subjects will be instructed to use a medically sound form of birth control during the study.

 Visit 2: Month 3 (90 days) ± 1 week (7 days)

 1. A clinician will ask subjects if they have experienced any changes in their health or
 taken new/adjusted current medications since the last visit. If an AE or SAE is
 reported, the examining Investigator will be informed and the appropriate forms will be
 completed.

 2. The test product will be collected and counted for compliance. Subjects found to be
 consistently out of compliance will be reminded of the correct usage instructions.

 3. Subjects will receive a brief physical exam. The physical will include vital signs
 (pulse and blood pressure).

 4. Subjects will complete the Women's Hair Loss Quality of Life Questionnaire (see Appendix
 VII), the Self-Assessment Questionnaire (see Appendix VIII) and the Subject Treatment
 Satisfaction and Ease of Use Questionnaire (see Appendix IX).

 5. Subjects will have their hair assessed by the Blinded Investigator for Hair Growth and
 Hair Quality (see Appendix V).

 6. Subjects will have 2D digital photography of the entire head/hair region for overall
 general hair growth and fullness ( see Appendix I).

 7. Subjects will have their scalp prepared for digital macrophotography and target area
 measurements done (see Appendix II).

 8. Subjects will have the selected target area (1cm x 1cm) photographed (see Appendix II).

 9. Subjects will have the extended target area (2cm x 2cm) bundle of hair measured for Hair
 Mass Index (HMI) (see Appendix III).

 10. Subjects will have ten (10) terminal hairs in a selected test site cut at the base of
 the scalp and the diameter of the hairs measured (see Appendix IV).

 11. Subjects will be dispensed a three (3) month supply of the test product (NUTRAFOL®
 supplement or Placebo, as randomized) and given written and verbal Usage and Lifestyle
 instructions (see Appendix X) and a calendar of future visits. Subjects will be
 instructed to ingest the test product per Sponsor instructions.

 Visit 3: Month 6 (180 days) ± 1 week (7 days)

 1. A clinician will ask subjects if they have experienced any changes in their health or
 taken new/adjusted current medications since the last visit. If an AE or SAE is
 reported, the examining Investigator will be informed and the appropriate forms will be
 completed.

 2. The test product will be collected and counted.

 3. Subjects will receive a brief physical exam. The physical will include vital signs
 (pulse and blood pressure).

 4. Subjects will complete the Women's Hair Loss Quality of Life Questionnaire (see Appendix
 VII), the Self-Assessment Questionnaire (see Appendix VIII) and the Subject Treatment
 Satisfaction and Ease of Use Questionnaire (see Appendix IX).

 5. Subjects will have their hair assessed by the Blinded Investigator for Hair Growth and
 Hair Quality (see Appendix V).

 6. Subjects will have 2D digital photography of the entire head/hair region for overall
 general hair growth and fullness (see Appendix I).

 7. Subjects will have their scalp prepared for digital macrophotography and target area
 measurements done (see Appendix II).

 8. Subjects will have the selected target area (1cm x 1cm) photographed (see Appendix II).

 9. Subjects will have the extended target area (2cm x 2cm) bundle of hair measured for Hair
 Mass Index (HMI) (see Appendix III).

 10. Subjects will have ten (10) terminal hairs in a selected test site cut at the base of
 the scalp and the diameter of the hairs measured (see Appendix IV).

 All primary and secondary parameters will be collected at Visits 1, 2 and 3. Missing data
 values will be minimized by intensive training of the interviewers in techniques of
 clarifying answers and checking questionnaires while participants are on-site. When missing
 values are identified, several approaches such as rescheduled within 24 hours of completion
 of tests or interviews will be employed to acquire the necessary data. Missing data will be
 also examined to assess randomness. Descriptive statistics will be obtained for all
 variables, tests of normality of continuous measures will be made and data will be examined
 for homogeneity of variance. An appropriate statistical method will be employed to correct
 for any abnormalities. The comparability of the two treatment groups in baseline demographic
 and clinical features will be tested with analyses of variance (ANOVAs) for continuous
 variables and Chi-square analyses for dichotomous variables. Initially, groups will be
 compared across all three visits for overall interaction effect. For any outcome with
 significant two-way interaction, group differences from baseline Visit to other two visits
 will be tested using analyses of variance with repeated measurements. These analyses were
 performed using the SPSS version 19. All analyses were two-tailed, where applicable, with
 p-value of 0.05 or less is obtained but other p-values may be evaluated on a case-by-case
 basis
Inclusion Criteria:

 1. Females, ages 21-65 years of age.

 2. Clinically-determined general good health as determined by responses to the initial
 study assessment.

 3. Females with self-perceived thinning hair as determined on initial study assessment by
 the Investigator (This will not include patients with medically diagnosed telogen
 effluvium).

 4. Females willing to maintain their normal hair shampooing frequency.

 5. Females willing to add the provided oral supplement to their current daily routine.

 6. Females willing to not substantially change their current diet, medications, or
 exercise routines for the duration of the study. If a subject receives physician
 guidance during the study to change diet, medications, or exercise routine, the
 subject will need to notify the clinic as soon as possible.

 7. Females willing to undergo a brief physical exam to include height, weight, blood
 pressure, pulse, general physical findings and a scalp exam. The physical exam will
 occur at Visits 1, 2 and 3.

 8. Women of child bearing potential should be willing to have a urine pregnancy test and
 will comply with a medically sound contraception method (including barrier control,
 abstinence, etc.). Women who are on birth control should have been on it for at least
 6 months and willing to continue the same method of birth control. The initiation of
 birth control should not have been associated with the initiation of hair
 loss/thinning.

 9. Females with Fitzpatrick I-IV photo skin types.

 10. Willingness to have 2D digital photography of the entire head/hair region for overall
 evaluation of general hair growth and fullness at Visits 1, 2 and 3.

 11. Willingness to have digital macrophotography of the target area and scalp for hair
 counts at Visits 1, 2 and 3.

 12. Willingness to have a bundle of hair measured by the Hair Check device for Hair Mass
 Index (HMI) at Visits 1, 2 and 3.

 13. Willingness to have ten (10) terminal hairs from the target area cut at the base of
 the scalp for microscopic hair measurements at Visits 1, 2 and 3.

 14. Willingness to maintain a consistent hair cut and hair color throughout the 6 month
 study period and to come to visits with clean, dry hair.

 15. Willingness of subjects who have color treated hair to have the color treatment
 performed at the same time interval prior to each visit (ie. If on Visit 1 the color
 treatment was done one week prior then the color treatment is expected to occur at a
 similar interval of one week prior to Visits 2 and 3).

 Exclusion Criteria:

 1. Females with any known allergy or sensitivity to any shampoo/conditioner.

 2. Females who are nursing, pregnant, planning to become pregnant during the study.

 3. Females with known stressful incident within the last six months (ie. death in family,
 miscarriage)

 4. Females who are participating on any clinical research study at ASIRC or at another
 research center or doctor's office.

 5. Females who have recently (within the last 6 months) started the use of hormones for
 birth control or hormone replacement therapy (HRT). Women currently using hormones for
 birth control or HRT must have been on a stable dose (6 months or longer) in order to
 be eligible for the study (the initiation of HRT or birth control should not have been
 associated with the initiation of hair loss/thinning).

 6. Females currently using any Low Level Laser Therapy (LLLT) to treat thinning hair.

 7. Females who have regularly used Rogaine (Minoxidil) within the last 3 months.

 8. Females who have used prescription drugs known to affect the hair growth cycle within
 the last 6 months (e.g., hormone-based birth control for less than 6 months,
 cyproterone acetate, aldactone/spironolactone, Finasteride or any 5-alpha-reductase
 inhibitor).

 9. Females suffering from other hair loss disorders, such as alopecia areata, scarring
 alopecia, androgenetic alopecia and telogen effluvium as determined on initial study
 assessment by the Investigator.

 10. No history of burning, flaking, itching, and stinging of the scalp.

 11. History of malignancy (except scc and bcc skin cancers) or undergoing chemotherapy or
 radiation treatments.

 12. A known history of autoimmune thyroid disease, any other thyroid disorder/abnormality
 or other autoimmune disorders that are not controlled in the opinion of the
 investigator may interfere with the study treatment.

 13. A known history of depression or bi-polar disease or any other condition that may
 impact the subject's participation.

 14. Is involved in any injury litigation claims.

 15. Known history or recent blood work indicating iron deficiency, bleeding disorders or
 platelet dysfunction syndrome as well as subjects taking anticoagulant therapy,
 antiplatelet medications, more than one (1) 325 mg ASA on a daily basis or smokers
 with usage >20 cigarettes/day.

 16. Individuals with self-reported uncontrolled diseases (i.e. diabetes, hypertension,
 hyperthyroidism, hypothyroidism, etc.). Medical conditions that are under control with
 or without treatment will be considered on an individual basis by the Investigator.

 17. Females with self-reported active hepatitis, immune deficiency, HIV or autoimmune
 disease.

 18. Females having a known active dermatologic condition which, in the opinion of the
 examining Investigators, might place the subject at a greater risk or interfere with
 clinical evaluations (e.g., seborrheic dermatitis, psoriasis, atopic dermatitis,
 advanced skin cancer, etc.).

 19. Use of any medications that are known to potentially cause hair loss or affect hair
 growth, as determined by PI.