Effect of GABA Supplementation in the Progression of Type 1 Diabetes in Children (GABA)

Double Blinded, Placebo Controlled Trial on the Effect of GABA Supplementation in the Progression of Type 1 Diabetes in Children

Type 1 diabetes mellitus (T1DM) is an autoimmune disease in which the body's immune system attacks and destroys the insulin producing beta cells of the pancreas. This condition is very prevalent, affecting up to 1:400/500 persons worldwide. Type 1 diabetes, previously known as juvenile diabetes, usually strikes in childhood, adolescence, or young adulthood, but lasts for a lifetime. To date, there have been no treatments that can arrest or reverse the ongoing beta cell destruction. The patients affected by this disease require multiple daily insulin injections to manage their blood sugars and usually have trouble regulating their blood sugars. Moreover, they are at risk for heart disease, kidney failure, eye problems, and other complications from this life-long condition.

The investigators plan to utilize gamma-amino butyric acid (GABA) in children with newly diagnosed T1DM. This neurotransmitter is made in the brain from the amino acid glutamate with the aid of vitamin B6. There have been some recent studies in diabetic mice utilizing GABA to reverse inflammation on the pancreas and improve hyperglycemia. GABA studied in healthy human subjects demonstrated that large oral doses of GABA increased insulin secretion from the pancreas.

The investigators propose that GABA given to children with new onset T1DM will be able to increase insulin production, suppress glucagon release, and decrease the inflammation surrounding the pancreas. The investigators hope this will at least prolong the beta cell life after diagnosis, if not lead to a cure for type 1 diabetes.

Study Overview

• Status: Withdrawn
• Conditions: Diabetes Mellitus
• Intervention / Treatment: Drug: gamma-amino-butyric acid; Dietary supplement: Xylitol

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Positive for any of the 3 measured antibodies GAD-65, ICA-512, or islet cell
• Must meet the ADA criteria for diabetes diagnosis
• Within 12 weeks of diagnosis of DMI at enrollment
• Peak stimulated c peptide of > 0.2 ng/mL with Mixed Meal Tolerance Test
• If post-menarchal they must use 2 forms of contraception during the study: this may include OCPs, abstinence and barrier methods. Abstinence will be accepted as a single method if used prior to enrollment.

Exclusion Criteria:

• Chronic systemic use of steroids
• Pregnancy or breastfeeding
• Seizure disorder
• Current use of Baclofen, Valium, Acamprosate, Neurontin, or Lyrica
• History of alcoholism/alcohol use
• Current use of anti diabetes drugs other than insulin
• Diagnosis of hemoglobinopathy
• Diagnosis of liver disease, cancer, cystic fibrosis, or renal failure

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GABA; 2/3 of participants will be randomized to the GABA treatment group. Dosage will be based on body weight and will be adjusted at each study visit.	Drug: gamma-amino-butyric acid; gamma-amino butyric acid will be administered orally at a dose of 80mg/kg/day divided BID for one year.; Other Names: GABA
Placebo Comparator: Placebo; 1/3 of participants will receive placebo.	Dietary supplement: Xylitol; The placebo group will be provided Xylitol powder dosed per body weight. Participants will be instructed to take powder orally twice a day for one year.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in stimulated c-peptide	We will measure c-peptide levels stimulated by a mixed meal tolerance test at baseline, six months and 12 months.	over 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in HbA1C	We will assess the change in hemoglobin A1C at baseline and every 3-4 months for a total duration of 1 year.	over 1 year
change in total daily insulin dose per kilogram	We will assess the change in total daily insulin dose per kilogram of subject body weight at baseline and every 3-4 months for a total duration of 1 year.	over 1 year

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Investigators: Principal Investigator: Alison J Lunsford, MD, University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Anticipated): April 1, 2013

Study Registration Dates

• First Submitted: March 16, 2012
• First Submitted That Met QC Criteria: March 22, 2012
• First Posted (Estimate): March 23, 2012

Study Record Updates

• Last Update Posted (Estimate): December 24, 2012
• Last Update Submitted That Met QC Criteria: December 21, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: children; diabetes mellitus
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Histamine Antagonists; Histamine Agents; Butyric Acid
• Other Study ID Numbers: UAB-GABA