Autism Spectrum Disorder (ASD) Neurodevelopmental Disorder With Issues Social Behavior, Communication Issues, GI Dysfunction. Study is Multimodal Interventions Targeting These Pathways With cSVF, Stored MSCs, FMT and Diet Modification. Role of Autoimmunity, Gut-brain Issues, & Issues Examined. (GARM-Autism)

Autism Spectral Disorder (ASD) In Adolescent-Adults Treated by Multimodal Protocol: IV Autologous cSVF, Interval IV Autologous MSCs (Cryopreserved), Strick Ketogenic Diet RESET Program, and Fecal Microbiota Transplantation (FMT)

Autism spectrum disorder (ASD) is a neurodevelopmental condition with core deficits in social communication and behavior, often accompanied by gastrointestinal (GI) and metabolic dysfunction. Emerging evidence supports the role of neuroinflammation (including autoimmune components), gut-brain axis disruption, and metabolic dysregulation in ASD pathophysiology. Multimodal interventions targeting these pathways-using autologous cSVF, cryopreserved MSCs, FMT, and dietary modulation-intent is that these multimodal interventions may offer synergistic benefits for adolescents and adults with ASD.

Study Overview

• Status: Enrolling by invitation
• Conditions: Autism Spectrum Disorder; Autism; Autism Spectral Disorder
• Intervention / Treatment: Procedure: Autologous MSC isolation, concentration, and cryopreservation of adult mesenchymal stem cells; Dietary supplement: Fecal Biomicrome Transplantation (FMT); Dietary supplement: Ketogenic RESET Diet Protocol; Behavioral: Trial combines use of cSVF and MSCs (cryopres) with diet modification and FMT (fecal material Transplant in adult ASD patients; Dietary supplement: FMT (Fecal Material Tranplantation); Biological: Use autologous cSVF + MSCs (cryo) for management of autoimmune component, anti-inflammatory and immune modulation

Detailed Description

This refined protocol integrates the latest evidence for a multimodal intervention-autologous cSVF, cryopreserved autologous MSCs, FMT, and a structured ketogenic protocol program-for adolescent and adult ASD management.

1. Protocol Summary

   Title:

   A Phase 1-2 Randomized Controlled Trial Evaluating the Safety and Efficacy of Multimodal Therapy (Autologous cSVF + Cryopreserved Autologous MSCs, Fecal Microbiota Transplantation, Ketogenic Program Reset, and OT/PT Training) in Adolescents and Adults with Autism Spectrum Disorder (ASD-Multi-level scoring)

   Sponsor: Blacktie Principal Investigator: Robert W. Alexander, MD, FICS Study Phase: Phase I/II Study Centers: 1-3 Clinical Applied Research Laboratories/academic centers with expertise in ASD, stem cell processing and utilization, plus gastroenterology/PMD consultants available for FMT in patient's locale

   Compliance:

   NIH and IRB oversight Informed consent for all participants

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2. Background and Rationale Autism spectrum disorder (ASD) is a neurodevelopmental condition with core deficits in social communication and behavior, often accompanied by gastrointestinal (GI) and metabolic dysfunction. Emerging evidence supports the role of neuroinflammation (including autoimmune components), gut-brain axis disruption, and metabolic dysregulation in ASD pathophysiology. Multimodal interventions targeting these pathways-using autologous cSVF, cryopreserved MSCs, FMT, and dietary modulation-may offer synergistic benefits for adolescents and adults with ASD.

   ________________________________________

3. Objectives and Endpoints

   Primary Objective:

   • Evaluate the safety and tolerability of the multimodal interventions compared to current standard of care (SOC) for supportive therapy.

   Secondary Objectives:

   • Assess changes in ASD core symptoms, GI function, behavioral and social outcomes, and quality of life.

   Endpoints:

   • Incidence of adverse events (AEs) and serious adverse events (SAEs)
   • Change in validated ASD and GI symptom scales (CARS, VABS-II, GSRS, SRS, ABC)
   • Microbiome diversity and metabolic biomarker changes
   • Assessed performance and QoL evaluations

4. Study Design and Methodology

   • Design: Multi-disciplined, open labelled, controlled, parallel-group (1:1:1), tracked for cellular and biologics used, open-label, including tracking of diet/OT-PT
   • Sample Size: 50 participants (range ages 10-90, DSM-5 ASD diagnosis)
   • Randomization: Stratified by age, sex, and baseline GI symptoms, Socialization
   • Interim Analysis: Futility analysis at 50% enrollment

5. Study Population

   Inclusion Criteria:

   • Age 10-90 years, DSM-5 ASD diagnosis
   • Stable on current medications (if so treated at time of selection)
   • With/without comorbid GI symptoms

   Exclusion Criteria:

   • Recent antibiotics/probiotics
   • Severe GI disease or malnutrition
   • Recent major surgery
   • Other Medical/Surgery issues that preclude the treatment with the protocol; including spectrum limitations for patient tolerance or compliance.

6. Intervention Protocols 6.1 Autologous Cellular Stromal Vascular Fraction (cSVF)

   • Collection: Small volume Lipoaspirate via sterile microcannula harvesting of small aggregate tSVF - under local or supplemental anesthesia as dictated by patient ability to tolerate.
   • Processing: Enzymatic digestion for cSVF and cellular isolation/concentration of heterogeneous cell groups within the cSVF (via collagenase, centrifugation, and possible undesignated cell characterization (CD34+, CD90+, CD105+)
   • Dosing: =/> 10 x 106 - 5 × 10^7 cells delivered by standard Normal Saline IV infusion
   • Administration: Intravenous (IV) route with in-line sterile 150u filtration
   • Applied LED Red Light Exposure cSVF throughout deployment
   • Standard American Cell Technology (ACT) protocol harvesting, testing and overnight shipping on day of Harvest for Cryopreservation Protocol for storage of autologous Mesenchymal Stem Cells (MSCs characterized as above) for future interval delivery
   • Safety: Monitored for infusion reactions, infection, and thromboembolic events] 6.2 Cryopreserved Autologous MSCs
   • Source: Autologous microcannula harvested tSVF or bone marrow (BMAC)
   • Cryopreservation: Slow freezing (-1°C/min to -80°C, then liquid nitrogen), 10% DMSO, clinical-grade solutions. ACT Standard and monitored storage per FDA requirement
   • Viability: ≥70% post-thaw, confirmed by ORFLO Flow Cytometry
   • Dosing: 1-30 × 10^6 cells within sterile Normal Saline (balanced) IV infusion minimum
   • Administration: Peripheral IV route with in-line 150 u micron filtration and Red Light Therapy
   • Quality Control: Surface marker analysis, sterility, [endotoxin, karyotype on record with FDA certified Cell Banking Laboratory- ACT] 6.3 Fecal Microbiota Transplantation (FMT)
   • Donor Screening: Pathogen, parasite, and virus screening; FDA GMP processing
   • Preparation: Standardized, frozen human gut microbiota, delivered on dry ice
   • Pre-treatment: 14 days oral vancomycin, bowel cleanse (MoviPrep), acid suppression (Prilosec)
   • Dosing: High initial dose (oral/rectal), followed by daily oral maintenance for 7-8 weeks
   • Monitoring: GI and behavioral symptoms (GSRS, CARS, SRS, VABS-II)14-17]] 6.4 Ketogenic/Carnivore Diet (Carnivore RESET Program)
   • Diet: High-fat, low-carbohydrate, animal-based reset; macronutrient ratios to induce a state of ketosis (indicative of fat burning and reduction of insulin resistance.
   • Baseline Blood Testing: FBS, Fasting Insulin Levels, Hemoglobin A1c, Lipid Panel, Fasting Ketones, CBC, CRP, and other appropriate testing
   • Monitoring: Dietary logs, blood ketones, nutritional assessments at least quarterly
   • Support: PMC, Gastroenterologist,etc Provider or Dietitian, compliance checks near patient's home
   • Repeat testing of Blood levels repeated at 90-180 days
   • Safety: Monitor for metabolic derangements, GI side effects 6.5 OT/PT Training
   • Program: Standardized occupational and physical therapy modules
   • Continuation of Verbal, Socialization, and Educational Efforts
   • Frequency: 2-3 sessions/week, individualized goals (may be home monitored)

7. Safety Monitoring Plan

   • Adverse Event Monitoring: Continuous, with prompt reporting of SAEs
   • Infusion Reactions: Pre- and post-infusion monitoring for autologous cSVF/MSCs
   • Dietary Safety: Regular metabolic and nutritional assessments and tracking
   • FMT Safety: Exclusion of high-risk participants, close monitoring for infection

8. Outcome Measures and Biomarker Assessments Domain Assessment Tools/Markers ASD Symptoms CARS, SRS, ABC, VABS-II; observational behavior, socialization changes, communication abilities, GI Symptoms Bristol Stool Scale; Management testing of bowel flora bacteria Metabolic Blood glucose, ketones, vitamin B6, dopamine Inflammation Fecal calprotectin, serum IgA, ESR/CRP Safety AE/SAE logs, laboratory monitoring

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9. Statistical Analysis Plan

   • Primary Analysis: Safety (AEs/SAEs) by intervention Provider
   • Secondary Analysis: Change in symptom scales and biomarkers (ANCOVA, mixed models)
   • Interim Analysis: Futility and safety at 50% enrollment check

10. Regulatory and Ethical Considerations

    • FDA/NIH Clinical Trial Submission: For Trial approval for use cSVF, MSCs, and FMT
    • IRB Approval: NIH/FDA Approval or equivalent recognized IRB Board (GARM International Review Board)
    • Informed Consent: All participants/guardians
    • Data Privacy: HIPAA-compliant data management

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Montana
    • Hamilton, Montana, United States, 59840
      • Regenevita Health
    • Hamilton, Montana, United States, 59840
      • Robert W. Alexander, MD, FICS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ADS
• Stable on current medications or therapy
• With/wthout comorbid GI (gut/Axis) symptoms

Exclusion Criteria:

• Recent antiobiotics or probiotic therapy within 30 days
• Severe GI disease or malnutrition
• Recent major surgery that may interfere with study course
• Other Med/Surgery issues that may preclude treatment with this protocol
• Inability to perform the monitoring of FMT without supervision by qualfied Provider

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: ASD behavior, learning, communication and diet; diet, bowel flora, autoimmune tracking, cSVF/MSC (cryo) multimodal approach

Procedure: Autologous MSC isolation, concentration, and cryopreservation of adult mesenchymal stem cells; Isolation/concentration autologous MSCs derived from tSVF from each patient participant only; Dietary supplement: Fecal Biomicrome Transplantation (FMT); Novel Biome Protocol for elimination of patient's gut flora, replacement oral transplantation with a known flora common to restore the brain-gut balance in ASD patients; Dietary supplement: Ketogenic RESET Diet Protocol; Limited timeframe strick ketogenic diet for RESET of insulin resistance in form of high animal derived protein, high animal derived fat, low carbohydrate diet for 90 days, then standard ketogenic diet as tolerated; Behavioral: Trial combines use of cSVF and MSCs (cryopres) with diet modification and FMT (fecal material Transplant in adult ASD patients; GI Axis modification of bowel flora (FMT); Diet modification to permit mild ketosis in patient; cellular modification with use of cSVF and MSCs (autologous only); Dietary supplement: FMT (Fecal Material Tranplantation); Converting diet from patient selection which complies with the needs to change the GI-Axis to accommodate bowel changes and restoration of a normal bowel flora; Biological: Use autologous cSVF + MSCs (cryo) for management of autoimmune component, anti-inflammatory and immune modulation; Use of cSVF isolation and submission to FDA certified tissue/cell bank for subsequent use of autolgous patient only

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Socialization Alterations	SRS-2 caregiver/teacher: Change in social behavior as measured by the Social Responsiveness Scale, Second Edition (SRS-2), a 65-item caregiver- and teacher-reported instrument scored on a scale of 0 to 195, where lower scores indicate better social functioning. SRS-2 assessments are completed at baseline, 3 months, 6 months, and 12 months to evaluate change over time.Time Frame: Baseline, 3 months, 6 months, and 12 months	1 year
Communication/Education Enhancement	PPVT-5 Peabody Picture Vocabulary testing: Change in receptive vocabulary and language comprehension as measured by the Peabody Picture Vocabulary Test, Fifth Edition (PPVT-5). Standard scores range from approximately 40 to 160 (mean = 100, SD = 15), where higher scores indicate better vocabulary and language ability. Testing is administered at baseline, 3 months, 6 months, and 12 months.Time Frame: Baseline, 3 months, 6 months, and 12 months	Months and 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gut-Brain Axis Improvement	GSRS Testing: Change in gastrointestinal symptoms as measured by the Gastrointestinal Symptom Rating Scale (GSRS), a 15-item patient- or caregiver-reported questionnaire. Scores range from 1 to 7 per item (total composite score 15-105), where lower scores indicate fewer or less severe GI symptoms. Assessed at baseline, 3 months, 6 months, and 12 months.Time Frame: Baseline, 3 months, 6 months, and 12 months	1 year

Collaborators and Investigators

• Sponsor: Black Tie Medical, Inc.

Publications and helpful links

General Publications

• Alexander, Robert W. Overview of COVID-19 Lung Damage Clinical Trial NCT#04326036 Using Cellular Stromal Vascular Fraction (cSVF) and Functional Respiratory Imaging (FRI) Analysis of Pulmonary Injury & Post-Viral (SARS-Cov-2) Adult Respiratory Distress Syndrome (ARDS). Ann Stem Cell Res Ther. 2020; 4(1): 1039.
• Alexander, Robert W. Overview of Cellular Stromal Vascular Fraction (cSVF) & Biocellular Uses of Stem/Stromal Cells and Matrix (tSVF + HD-PRP) in Regenerative Medicine, Aesthetic Medicine and Plastic Surgery. J. Stem Cell Res Dev Ther. 2019; 4:1-15.
• Alexander, Robert W., Everts, Peter A. Understanding Communication Between Cellular Stromal Vascular Fraction (cSVF), Mesenchymal Stem Cells (MSC), Pericytes, Blood Derivative (HD PRP): Mechanisms in Inflammation and Immune Modulation. 2026; J Stem Cell Res. 7(1)-81. DOI:http:doi.org/10.52793/JSCR.2026.7(7(1)-81.
• Liu, S., Li, E. et al. The gut microbiota regulates autism-like behavior by mediating vitamin B6 in EphB6-deficient mice. Microbiome. 2020; 8: 120.
• Sharon, G., Cruz, N.J., et al. Human gut microbiome from autism spectrum disorder promote behavioral symptoms in mice. Microbiome. 2019; 7: 3.
• Zuo, T., Kamm, M.A. et al. Fecal microbiota transplantation: indications, methods, evidence and future directions. Microbiome. 2017; 5:24.
• Effects, methods and limits of cryopreservation on mesenchymal stem cells. Stem Cell Res Ther. 2024; 5-24.
• Principles and Protocols for Post-Cryopreservation Quality Evaluation of Stem Cells in Novel Biomedicine. Cells. 2022; 11(9): 1563
• Quintero, A.J., et al. Evaluating the quality of studies reporting on clinical application of stromal vascular fraction: A systematic review and proposed reporting guidlines (CLINIC-STRA-SVF), J Transl Med. 2023; 21:456.
• Wragg, N.M. et al. Intern J Mol Sci. 2020: 21(22): 8579.
• Bradstreet, J.J. et al. Cell Transplant. 2014: 23:1 suppl): 105-112
• Chez, MG, et al. Stem Cells Transl Med. 2018: 7(7): 636-647
• Brinkman FSL, Winsor GL, Done RE, Filloux A, Francis VI, Goldberg JB, Greenberg EP, Han K, Hancock REW, Haney CH, Haussler S, Klockgether J, Lamont IL, Levesque RC, Lory S, Nikel PI, Porter SL, Scurlock MW, Schweizer HP, Tummler B, Wang M, Welch M. The Pseudomonas aeruginosa whole genome sequence: A 20th anniversary celebration. Adv Microb Physiol. 2021;79:25-88. doi: 10.1016/bs.ampbs.2021.07.001. Epub 2021 Nov 16.
• Quintero, A. J. et al. Evaluating the quality of studies reporting on clinical applications of stromal vascular fraction: A systematic review and proposed reporting guideline (CLINIC-STRA-SVF). J Transl Med. 2023; 21: 456.
• Nguyen, Thanh L., Nguyen, H.P, et al. Outcomes of autologous bone marrow mononuclear cell administration combined with educational intervention in the treatment of autism spectrum disorder: a randomize, open label, controlled phase II clinical trial. Stem Cell Res Ther. 2025; 15(1):404
• Nagpal, R., Neth, B.J et al. Modified Mediterranean-ketogenic diet modulates gut microbiome and short-chain fatty acids in association with alzheimer's disease markers in subjects with mild cognitive impairment. EBioMedicine. 2019: 47:529-542.
• Kang, D.W., Adams, JB, et al. Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptom: an open label study. Microbiome. 2017: 5 :10
• Galipeau, J, et al. J Translat Med, 2019: 17:397
• Xie, Y et al. Stem Cell Therapy in the Treatment of Patient with Autism Spectrum Disorder: a Systematic Review and Meta-analysis. Stem Cell Rev Rep. 2021; 17(5): 1769-1780.

Study record dates

Study Major Dates

• Study Start (Estimated): April 30, 2026
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): August 14, 2030

Study Registration Dates

• First Submitted: April 4, 2026
• First Submitted That Met QC Criteria: April 16, 2026
• First Posted (Actual): April 23, 2026

Study Record Updates

• Last Update Posted (Actual): April 27, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Socialization; Learning Disability; Situational awareness and communication; Bowel dysfunction (flora correction); cSVF and Cryopreserved MSCs (autologous)
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Digestive System Diseases; Gastrointestinal Diseases; Neurobehavioral Manifestations; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Communication Disorders; Pathological Conditions, Signs and Symptoms; Behavior; Signs and Symptoms; Autism Spectrum Disorder; Autistic Disorder; Intestinal Diseases; Learning Disabilities; Communication; Therapeutics; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Biological Therapy; Immune System Phenomena; Anti-Inflammatory Agents; Fecal Microbiota Transplantation; Immunomodulation
• Other Study ID Numbers: GARM-Autism Adults

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No