AGA Biocellular Stem/Stromal Hair Regenerative Study

Detailed Description:

The cosmetic discipline of hair restoration is rooted in numerous landmark studies and
progressive medical science in the medical literature. , , , , With the advent of advance
theories and science within the scope of regenerative medicine, numerous reports are noted in
the literature. , , , , , using biological modalities, e.g., HD-PRP concentrates defined as >
4-6 times patient circulating baselines, for stimulation of scalp tissues and hair follicles
in androgenetic alopecic (AGA).

Design of this study is intended to be a prospective, randomized, multicenter trial with
blinding of outcomes for independent observer, clinical provider and patient
observation/satisfaction studies. The study proposes adipose-derived (AD) biocellular
material when mixed with platelet high density concentrates (HD-PRP) offers a potential
advantage for a markedly more effective therapeutic profile in areas of follicular
miniaturization, tissue age related senescence, and effect the decreased vascular
capabilities by stimulation of vasculoneogenesis. The benefits of using autologous
adipose-derived stem/stromal cell (ADSCs) populations are cell proliferation and
vasculogenesis that is intrinsically linked with native immunomodulatory capacities. Reports
describing the safety and efficacy of this biocellular combination have been reported in peer
reviewed literature. , In the second and third arm of this study, the use of regenerative
protocols currently being utilized in the treatment of degenerative musculoskeletal
conditions is employed. These protocols feature the use of an emulsified AD-tSVF and
emulsified cell enriched AD-cSVF containing the full heterogeneous stem/stromal cell
population and matrix that is injected into the regions of scalp containing the
microenvironment (niche) of the hair follicle. In Arm 3, cellular enrichment of the
emulsified AD-tSVF is accomplished via a semi-automated, closed sterile system (Healeon
CentriCyte 1000 system) to isolate and concentrate AD-cSVF. The AD-cSVF is then mixed with
high-density platelet rich plasma (HD-PRP) concentrates and emulsified AD-tSVF tissues
(AD-tSVF) prior to scalp injection. This injected cell-enriched product contains native
adipose tissue scaffolding, autologous HD-PRP, and enriched adipose stem/stromal
cell-enriched concentration of stromal/stem cells (AD-cSVF).

The goal of this study is to demonstrate the safety and efficacy of the HD-PRP + AD-tSVF +
AD-cSVF biocellular injections into the scalp of men and women with a diagnosis of
non-scaring alopecias, with full reporting of AE and SAE (adverse events). The biocellular
material is injected 3-5 mm in depth within the mid-reticular dermis to upper subcutaneous
fat layer of the scalp for the purpose of regenerating the miniaturized hair follicle, and
delivering a milieu of stromal/stem cells that facilitate regenerative changes within the
tissue sites. In addition to providing tissue scaffolding, and a greater number of
stromal/stem cells to the tissues surrounding the follicular niche, the novel use and
emulsification of AD tissues with cell-enriched biocellular material permits ergonomic
facilitation of layered injection patterns in the scalp with small gauge (25-27 gauge)
needles This emulsified AD Biocellular methodology reduces injection pressure requirements
using smaller gauge needles. When clinically compared to the use of much larger needles
required to inject non-emulsified AD-tSVF, it is an improvement on current techniques.

Successful stem/stromal cell-enrichment of AD-tSVF and HD PRP biocellular mixture has been
reported in numerous peer-reviewed and published clinical experiences of injections for
structural tissue augmentation in plastic surgery, chronic wound therapies, and ultrasound
guided musculoskeletal treatments in orthopedic surgery. A "retrograde" filling technique
creating a potential space and subsequently injecting into this space the biocellular
material as the needle is withdrawn is advanced in this study.

All patients will undergo venipuncture for obtaining HD-PRP concentrates following FDA
approved Emcyte II manufacturer's guidelines. Those patients having biocellular treatment
with also undergo a small volume closed syringe microcannula lipoaspiration to acquire
AD-tSVF tissues, which will be emulsified via the Healeon ACM System per manufacturer's
guidelines. Cellular testing of samples in Arm 2 and Arm 3 will be performed by flow
cytometry (ORFLO, MoxiFlow, Ketchum, ID, USA) for viability and cell concentrations. The
trial will include the biocellular mixture of HD-PRP + emulsified AD-tSVF (Arm 2) and/or,
HD-PRP + emulsified AD-tSVF + AD-cSVF (Arm 3). Study will utilize a standardized high-density
PRP concentration system on all patients in the same volume. The definition of HD-PRP
concentrates is a minimum =/>4 times patient circulating platelet counts.

A detailed patient medical history, informed consent, and screening evaluation will determine
eligibility and candidacy for the study. Each patient will undergo a small volume
lipoaspiration (defined as <100 cc) under local anesthesia with, or without, oral sedation.
Candidates will be assigned to one of three treatment ARMs. The treatment ARMS are: ARM 1:
HD-PRP + Matristem Matrix (A-Cell) (control); ARM 2: HD-PRP + emulsified AD-tSVF; and, ARM 3:
HD-PRP + emulsified AD-tSVF + cell-enriched AD-cSVF. All patients will receive a standard
ring block local anesthesia of the scalp treatment areas, followed by retrograde injection
pattern of the biocellular material.

Recording of the platelet baseline and treatment concentrates, flow cytometric examination of
cell viability, and cell counts of AD-cSVF will be completed on each patient. Biocellular
injections and treatment will be given on two (2) separate procedures three (3) months apart.
Follow up clinical examinations are to be performed at 6 months and 1year period with
completion of outcomes analyses including independent observer, clinician, and subject
satisfaction. The volume of the HD-PRP concentrates will be the standardized in volume for
all trial ARMs.

Immediate reporting to the study group for all AR and SAR will be documented and recorded for
the safety records directly to Ken Williams, DO, as Principal Clinical Investigator. This
Clinical Trial will have a sample size of 60 patients at up to six (6) centers utilizing the
same protocols, equipment and reporting requirements.

Inclusion Criteria:

- Inclusion Criteria:

1. Males with a diagnosis of Androgenetic Alopecia (AGA).

2. Females with a biopsy proven diagnosis of Female Pattern Hair Loss (FPHL)
excluding scaring or autoimmune disorders.

3. Males with hair loss consistent with Grades II, III, IIIA, III-Vertex, IV, IV-A,
based on Norwood-Hamilton Scale.

4. Females with hair loss consistent with Grades I-3, I-4, II-1, II-2 based on the
Savin Scale.

5. Demonstrated ability to legally provide written informed consent and comply with
the study requirements

6. For women of childbearing potential with screening negative pregnancy test and
subject agrees to avoid pregnancy with two forms of contraception for the
duration of study

7. Subject is willing to maintain existing and consistent hair length and color.

8. Ability to complete study procedures, patient surveys, and photodocumentation.

9. Subject is ≥ 18 years of age.

10. Five (5) year cancer free period without treatment and no evidence of recurrence

Exclusion Criteria:

1. Subjects who have used oral spironolactone, finasteride, dutasteride, minoxidil, or
any oral or topical medication including over the counter and herbal medications for
the treatment of hair loss within 12 months of study screening.

2. Simultaneous treatment with an investigational product or procedure within 30 days, or
planned future participation in another clinical study

3. Subject has previously failed or has been deemed non-responsive to a previous
experimental hair loss treatment.

4. Subject must have no previous hair transplant, PRP, biocellular treatments, micro
needling, cold laser therapies, or any other scalp or hair loss treatment.

5. Subject with previously diagnosed or suspected of having active scaring alopecia,
autoimmune diseases such as serum lupus erythematosus, or alopecia areata; unspecified
dermatologic condition, or disorders that will make hair growth difficult (such as
systemic burns, etc.).

6. History of or active diagnosis of autoimmune disease or organ transplantation or
immunosuppressive medication(s).

7. Receiving active cancer treatment or have present or previous malignancies except a
history of squamous or basal skin cell carcinoma with excision for cure.

8. Active systemic infection at the time of enrollment. If acquired afterwards, exclusion
based on clinical judgment of investigator.

9. Use of chronic antibiotics and/or systemic corticosteroids.

10. Use of systemic agents that increase bleeding or clotting, or disorders associated
with these effects, including patients receiving GIIB/IIIa inhibitors in the 2 weeks
prior to the study procedure through to 1 week after the study procedure.

11. Clinically significant or current medical or psychiatric illness.

12. Prior surgery in the treatment area.

13. Any disease or condition (medical or surgical) that, in the opinion of the
investigator, might compromise dermatologic, hematologic, cardiovascular, pulmonary,
renal, gastrointestinal, hepatic, or central nervous system function; or any condition
that would place the subject at increased risk of increased morbidity or mortality.

14. Pregnant or lactating female, or women trying to become pregnant.

15. Known allergic reaction to components of study treatment and/or study injection
procedure

16. Subject has any disorder or any reason that may prevent compliance to study procedures
and visits.

17. Employees or family members of the study staff.

18. Untreated or uncontrolled thyroid disorder (abnormal TSH/free T4) or diabetes mellitus
(HgbA1C > 8.0).

19. Subject who has a sensitive, irritated, or abraded scalp area.

20. Women who have an alternate diagnosis that is associated with hair loss.

21. Clinically significant abnormal findings on laboratory screening panels:

- Hemoglobin ≤ 10 g/dL

- Hepatic dysfunction, as defined as aspartate aminotransferase (AST), alanine
aminotransferase (ALT), or bilirubin levels > 1.5 times the upper limit of normal
range prior to randomization.

- Chronic renal insufficiency as defined as a serum creatinine > 1.2 mg/dL for
women and > 1.5 mg/dL for men.

- An elevated PT/PTT, INR,

- platelet count < 100 x 109/L

Exclusion Criteria: