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

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

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.

Study Overview

• Status: Unknown
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Drug: Placebo; Drug: Gamma Aminobutyric Acid (GABA)

Detailed Description

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

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200040
      • Recruiting
      • Department of Endocrinology and Metabolism，Huashan hospital
      • Contact: Zhaoyun Zhang; Phone Number: 86-21-52888286
      • Contact: Yi Wang; Phone Number: 86-21-52887022
      • Principal Investigator: Yiming Li
      • Principal Investigator: Qinghua Wang, Doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 19 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Be between the ages of 5 and 21 years*
2. Be within 6-months of diagnosis of type 1 diabetes based on American Diabetes Association (ADA) criteria
3. 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
4. Presence of at least one diabetes-related autoantibody
5. Must be willing to comply with intensive diabetes management and monitor glucose with glucometer.
6. 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
7. Parents and participants must sign the informed consent

Exclusion Criteria:

1. Be currently pregnant or lactating or anticipate getting pregnant during the study period.
2. Type 2 diabetes and other specific types of diabetes.
3. Require use of systemic immunosuppressant, steroids or other medications that can affect glucose metabolism.
4. Have a history of malignancies
5. Be currently using non-insulin pharmaceuticals to affect glycemic control
6. Have any acute or chronic complicating medical issues or abnormal clinical laboratory results that interfere with study conduct or cause increased risk.
7. Have a history of epilepsy, significant head trauma or cerebrovascular accident or clinical features of continuous motor unit activity in proximal muscles
8. Inability or unwillingness to comply with the provisions of this protocol
9. Have an active infection or positive PPD test result.
10. Have serologic evidence of current or past HIV, Hep B, or Hep C infection.
11. Be with acute complications of diabetes (diabetic ketoacidosis, nonketotic hypersmolar coma, diabetic lactic acidosis)
12. Have a history of chronic renal failure, serum creatinine higher than 177umol/L
13. Have a history of impaired liver function, ALT or AST level elevated more than (or equal to) 2.5 times of upper limmit normal.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Daily dosage of insulin (units/kg).	The study will assess the daily dosage of insulin (units/kg).	baseline and up to 52 weeks

Collaborators and Investigators

• Sponsor: Huashan Hospital
• Investigators: Principal Investigator: Yiming Li, Doctor, Huashan Hospital; Principal Investigator: Qinghua Wang, Doctor, St Michale's Hospital, University of Toronto

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Anticipated): December 1, 2014
• Study Completion (Anticipated): December 1, 2014

Study Registration Dates

• First Submitted: January 12, 2013
• First Submitted That Met QC Criteria: January 31, 2013
• First Posted (Estimate): February 1, 2013

Study Record Updates

• Last Update Posted (Estimate): February 1, 2013
• Last Update Submitted That Met QC Criteria: January 31, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; GABA Agents; gamma-Aminobutyric Acid
• Other Study ID Numbers: 2012-024