Effects Of Gamma Aminobutyric Acid On The Progression Of New Onset Juvenile Type 1 Diabetes

Study Overview
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Brief Summary
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This study is a multicenter, randomized, double-masked, placebo-controlled clinical study. All groups will receive standard intensive diabetes treatment with insulin and life style management. 60 subjects will be randomly assigned in a 1:1:1 ratio to receive placebo or different dosage of GABA. GABA is an amino acid produced from glutamate by glutamic acid decarboxylase. It was approved for the treatment of hepatic coma, fibromyalgia, ataxia in China and is widely used as supplement for the treatment of epilepsy, insomnia, stress and tobacco dependence. It has been recently shown that GABA can prevent and reverse the development of diabetes in type 1 mice models. Participants will receive placebo or GABA for 52 weeks. The study will consist of 4 weeks screening period, 2 weeks run-in period, 52 weeks treatment period and 4 weeks follow-up period. Enrollment is expected to occur over 2 years. To assess the efficacy and safety of GABA for the treatment of juvenile type 1 diabetes in new onset subjects.

Detailed Description
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Primary Outcome: The primary statistical hypothesis to be assessed in this study is whether the mean C-peptide value for study subjects receiving GABA differs significantly from the mean value for placebo subjects assessed at follow-up. Secondary Outcome: The study will examine the HbA1C and the daily dosage of insulin (units/kg). Exploratory Endpoint: The study will assess the effects of treatment on inflammatory markers and immunological outcomes. Major Inclusion Criteria: Type 1 diabetes within past 6 months Age 5-21 years* At least one diabetes associated autoantibody

Official Title
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Effects Of Gamma Aminobutyric Acid On The Progression Of New Onset Juvenile

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Drug: Gamma Aminobutyric Acid (GABA)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be between the ages of 5 and 21 years* Be within 6-months of diagnosis of type 1 diabetes based on American Diabetes Association (ADA) criteria Must have stimulated C-peptide levels ≥0.2 pmol/ml measured during a mixed meal tolerance test (MMTT) conducted at least 21 days from diagnosis of diabetes and within one month of randomization Presence of at least one diabetes-related autoantibody Must be willing to comply with intensive diabetes management and monitor glucose with glucometer. If participant is female with reproductive potential, she must be willing to avoid pregnancy during the whole study period and have a negative pregnancy test Parents and participants must sign the informed consent Exclusion Criteria: Be currently pregnant or lactating or anticipate getting pregnant during the study period. Type 2 diabetes and other specific types of diabetes. Require use of systemic immunosuppressant, steroids or other medications that can affect glucose metabolism. Have a history of malignancies Be currently using non-insulin pharmaceuticals to affect glycemic control Have any acute or chronic complicating medical issues or abnormal clinical laboratory results that interfere with study conduct or cause increased risk. Have a history of epilepsy, significant head trauma or cerebrovascular accident or clinical features of continuous motor unit activity in proximal muscles Inability or unwillingness to comply with the provisions of this protocol Have an active infection or positive PPD test result. Have serologic evidence of current or past HIV, Hep B, or Hep C infection. Be with acute complications of diabetes (diabetic ketoacidosis, nonketotic hypersmolar coma, diabetic lactic acidosis) Have a history of chronic renal failure, serum creatinine higher than 177umol/L Have a history of impaired liver function, ALT or AST level elevated more than (or equal to) 2.5 times of upper limmit normal.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Gamma Aminobutyric Acid (GABA)<br>GABA will be given 50mg/kg/Day, thrice daily for 52 weeks | Drug: Gamma Aminobutyric Acid (GABA)<br>* two dosages will be used in this study. GABA: 50mg/kg/day and 100mg/kg/day<br>* Other names: Gamma Aminobutyric Acid;|
| Active Comparator: Gamma Aminobutyric Acid GABA)<br>GABA will be given 100mg/kg/Day, thrice daily for 52 weeks. | Drug: Gamma Aminobutyric Acid (GABA)<br>* two dosages will be used in this study. GABA: 50mg/kg/day and 100mg/kg/day<br>* Other names: Gamma Aminobutyric Acid;|
| Placebo Comparator: placebo<br>placebo will be given thrice daily for 52 weeks | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| C-peptide value | The primary statistical hypothesis to be assessed in this study is whether the mean C-peptide value for study subjects receiving GABA differs significantly from the mean value for placebo subjects assessed at follow-up. | baseline and up to 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HbA1C level | The study will examine the HbA1C level every 3 months from baseline and up to 52 weeks. | baseline and up to 52 weeks |