The Use of Glutamic Acid Decarboxylase (GAD) and Gamma-Amino Butyric Acid (GABA) in the Treatment of Type I Diabetes

NCT02002130 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: GABA-GAD
• Study Type: interventional
• Target: 101
• Locations: 1 country
• Sites: 1

Brief Summary

Type I Diabetes is an auto immune disease in which the body's immune system attacks and destroys the insulin-producing beta cells of the pancreas. Therefore, children affected by this condition present with high blood sugars. This condition affects 1:400/500 persons worldwide.Type I Diabetes, previously known as Juvenile Diabetes,usually strikes in childhood, adolescence, or young adulthood, but lasts for a lifetime. To date, there has been no treatments that can arrest, or reverse the ongoing beta cell destruction. We hypothesize that GABA, a naturally occurring substance, has the potential to reduce the inflammation and protect the pancreatic beta cells from autoimmune destruction. GAD-alum may contribute to the preservation of residual insulin secretion in patients with recent onset, Type I Diabetes.

Conditions

Type I Diabetes

Keywords

Diabetes

Outcome Measures

Primary Outcomes (1)

• Compare the effect of oral GABA or oral GABA/GAD combination administration on pancreatic beta cell function by quantitative C-peptide secretion

  This will be assessed by meal stimulated c-peptide secretion in treatment cohorts compared to age matched placebo controls before and after 1 year of treatment.

  12 months after baseline

Secondary Outcomes (4)

• Compare the effect of oral GABA or GABA/GAD administration on fasting and meal stimulated glucagon and pro-insulin levels.

  12 months after baseline

• Compare the effect of oral GABA or GABA/GAD administration on total daily insulin usage by participants and corrected Hemoglobin A1C.

  12 months after baseline

• Compare the effect of oral GABA or oral GABA/GAD administration on indices of immune system function.

  12 months after baseline

• Compare the effect of oral GABA or oral GABA/GAD administration on diabetes related autoantibodies

  12 months after baseline

Study Arms (3)

Placebo GABA and Placebo GAD-alum

PLACEBO COMPARATOR

Placebo formulation, Maltodextrin, for Gamma-Amino Butyric Acid (GABA) capsule-identical in appearance and taste, but no active medication will be taken with meals.Number of pills based on body surface area. Placebo GAD-alum(Glutamic Acid Decarboxylase in alum) injection- identical in appearance but no active medication will be received at baseline and 1 month.

Drug: Placebo GABA and Placebo GAD-alum

GABA and placebo GAD-alum

ACTIVE COMPARATOR

Patients will receive the Active GABA (Gamma-Amino Butyric Acid) capsules. Each capsule 250mg. Dosage will be calculated according to body surface area of the child and divided between 2 meals/day. Larger dose taken with larger meal. Patients will receive the GAD-alum( Glutamic Acid Decarboxylase in alum) placebo at baseline and 1 month.

Drug: GABA and Placebo GAD-alum

Active Oral GABA and Active GAD-alum Injection

ACTIVE COMPARATOR

Patients will receive Oral GABA(Gamma-Amino Butyric Acid) 250mg capsules. Dosage (# of capsules) based on body surface area and divided between 2 meals/day. Patients will receive a primary (at baseline)injection of recombinant human GAD(Glutamic Acid Decarboxylase) in a standard vaccine formulation with alum, and a booster injection of the same at 1 month after baseline.

Drug: Active Oral GABA and Active GAD-alum injection

Interventions

Placebo GABA and Placebo GAD-alum DRUG

Maltodextrin as a placebo formulation for GABA Placebo GAD-alum injection

Also known as: Placebo for Gamma-Amino Butyric Acid

Placebo GABA and Placebo GAD-alum

GABA and Placebo GAD-alum DRUG

Oral Active GABA with Placebo GAD-alum

GABA and placebo GAD-alum

Active Oral GABA and Active GAD-alum injection DRUG

Active Oral GABA and Active GAD-alum injection

Active Oral GABA and Active GAD-alum Injection

Eligibility Criteria

• Age: 4 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients must be positive for GAD-65 antibody.
• They must meet ADA criteria for diabetes: classic symptoms, plus blood sugar \> 200mg/dL or fasting blood sugar \> 126 mg/dL.
• Must be enrolled with 5 weeks of diagnosis
• Females who are post-menarchal must use 2 forms of contraception if not abstinent. The types of contraception deemed acceptable would be oral contraceptives, intrauterine devices, and barrier methods.
• Signed informed consent form.

You may not qualify if:

• Chronic systemic steroid use, including inhaled compounds, or any medication which can alter glucose metabolism
• Obesity, defined as BMI \> 95% or BMI \> 27 in adolescents with acanthosis score between 1-1.5.
• Pregnant and/or breast feeding
• History of seizure disorder
• Patients on medications that may disturb GABA action, such as Baclofen, Valium, Acamprosate, Neurontin, or Lyrica
• history of any alcoholism or substance abuse.
• Chronic Disease (such as liver, cancer, cystic fibrosis, or renal failure)
• Chromosome abnormality (such as Trisomy 21, Turner Syndrome, etc.)

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• Diamyd Inc: collaborator
• NOW Foods: collaborator
• Janssen Pharmaceuticals: collaborator
• Juvenile Diabetes Research Foundation: collaborator

Study Sites (1)

Children's of Alabama

Birmingham, Alabama, 35233, United States

Location

Related Publications (4)

• Ludvigsson J, Faresjo M, Hjorth M, Axelsson S, Cheramy M, Pihl M, Vaarala O, Forsander G, Ivarsson S, Johansson C, Lindh A, Nilsson NO, Aman J, Ortqvist E, Zerhouni P, Casas R. GAD treatment and insulin secretion in recent-onset type 1 diabetes. N Engl J Med. 2008 Oct 30;359(18):1909-20. doi: 10.1056/NEJMoa0804328. Epub 2008 Oct 8.

  PMID: 18843118 BACKGROUND

• Soltani N, Qiu H, Aleksic M, Glinka Y, Zhao F, Liu R, Li Y, Zhang N, Chakrabarti R, Ng T, Jin T, Zhang H, Lu WY, Feng ZP, Prud'homme GJ, Wang Q. GABA exerts protective and regenerative effects on islet beta cells and reverses diabetes. Proc Natl Acad Sci U S A. 2011 Jul 12;108(28):11692-7. doi: 10.1073/pnas.1102715108. Epub 2011 Jun 27.

  PMID: 21709230 BACKGROUND

• Heath KE, Feduska JM, Taylor JP, Houp JA, Botta D, Lund FE, Mick GJ, McGwin G Jr, McCormick KL, Tse HM. GABA and Combined GABA with GAD65-Alum Treatment Alters Th1 Cytokine Responses of PBMCs from Children with Recent-Onset Type 1 Diabetes. Biomedicines. 2023 Jul 10;11(7):1948. doi: 10.3390/biomedicines11071948.

  PMID: 37509587 DERIVED

• Freese J, Al-Rawi R, Choat H, Martin A, Lunsford A, Tse H, Mick G, McCormick K. Proinsulin to C-Peptide Ratio in the First Year After Diagnosis of Type 1 Diabetes. J Clin Endocrinol Metab. 2021 Oct 21;106(11):e4318-e4326. doi: 10.1210/clinem/dgab463.

  PMID: 34228132 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus

Interventions

gamma-Aminobutyric Acid

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Kenneth McCormick, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

• Gail Mick, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: November 18, 2013
• First Posted: December 5, 2013
• Study Start: January 1, 2015
• Primary Completion: October 15, 2021
• Study Completion: April 15, 2022
• Last Updated: May 6, 2022

Record last verified: 2022-05

Locations

US (1)