GABA Treatment in Subjects With Type 1 Diabetes

Study Overview
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Brief Summary
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test if a food supplementation with GABA can improve insulin production capacity in type 1 diabetes patients by turning alfa cells into beta cells in accordance with mice and cell studies.randomised parallel study with placebo as control

Detailed Description
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our results indicate that alfa-cells can be regenerated and used to regenerate functional beta-like cells in vivo in type 1 diabetes models. Aiming to eventually apply these findings to type 1 diabetic patients, we initiated multiple screens seeking for compounds inducing alfa-to-beta-cell conversion. Using the mouse as a model, we thereby found that GABA (gamma-aminobutyric acid) could promote a cycle of conversion of alfa-cells into functional beta-like cells,GABA being considered as a non-harmful food supplement, one could envision a trial in type 1 diabetic patients. Indeed, a putative cure for type 1 diabetes may include halting the autoimmune insult to the pancreatic beta-cells and restoring insulin secretion by expanding beta-cell mass by beta-cell-regeneration and/or preventing beta-cell apoptosis induced by cytokines. Immunosuppression initiated at the onset of type 1 diabetes has been shown to preserve beta-cell function, but is associated with significant toxicities. Other studies using nicotinamide and parenteral insulin have failed to prevent development of type 1 diabetes. Objectives Primary objective: To investigate the effect and safety of the dietary supplement GABA provided at a dose of 6 g daily compared to placebo for 12 weeks on change in beta-cell function in patients with C-peptide negative type 1 diabetes as an adjunctive therapy to insulin treatment. Population A total of 30 patients with C-peptide negative type 1 diabetes, randomised 2:1 GABA: Placebo. Intervention After randomisation patients are treated with the dietary supplement GABA or matching placebo, titrated to 3 x 2g, or maximum tolerated dose, for 12 weeks. The insulin dose is reduced if needed according to Self-monitored blood glucose (SMBG) and hypoglycaemic episodes.

Official Title
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A Randomised, Double-blind, Placebo-controlled, Parallel Group, Single-centre Trial of GABA Treatment in Subjects With Type 1 Diabetes

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Dietary Supplement: Gama amino butyric acid (GABA)
* Dietary Supplement: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria:stimulated c peptide <0.03 mmol/l type 1 diabetes - Exclusion Criteria: • Type 2 diabetes Fertile women not using chemical (tablet/pill, depot injection of progesterone, subdermal gestagen implantation, hormonal vaginal ring or transdermal hormonal patch) or mechanical (spirals) contraceptives Pregnant or nursing women Cancer unless in complete remission for > 5 years Treatment with oral glucocorticoids Hypoglycaemia unawareness (unability to register low blood glucose) Known or suspected hypersensitivity to trial product or related products Abuse of alcohol or drugs, or any other co-existing condition that would make patients unsuitable to participate in the study, as deemed by the investigators Receipt of an investigational drug within 30 days prior to visit 0 Simultaneous participation in any other clinical intervention trial Chronic systemic use of steroids Seizure disorder Current use of Baclofen, Valium, Acamprosate, Neurontin, or Lyrica

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: randomised controlled study with active compared to placebo for 12 weeks
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: GABA<br>gamma Amino butyric acid (GABA) food supplement with 6 g per day | Dietary Supplement: Gama amino butyric acid (GABA)<br>* food supplement Gama amino butyric acid (GABA) as capsules<br>* Other names: gaba;|
| Placebo Comparator: PLACEBO<br>Matching placebo capsules to GABA | Dietary Supplement: placebo<br>* matching placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| insulin production | c peptide production during meal stimulation | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| c peptide response (change from fasting baseline to meal stimulated concentration in blood) | maximal c peptide change from baseline during meal testing with sustacal, | after 12 weeks | 
| c peptide response beta cell | beta cell sensitivity during meal testing, calculated with Homeostatic Model assessment b (HOMAb) | after 12 weeks | 
| glucagon response | increase in blood glucagon concentration from fasting to peak during meal testing, | after 12 weeks | 
| metabolic parameters | hba1c (mmol/mol) change from baseline | 12 weeks | 
| metabolic parameters dose of insulin | insulin dose used pr 24 hours | 12 weeks | 
| metabolic parameters glucose | hypoglycemia,(number of events of severe and mild hypoglycemia self reported) | 12 weeks | 
| metabolic parameters lipid | lipid (LDL cholesterol ) (mmol/l) | 12 weeks | 
| metabolic parameters weight | body weight (kg) | 12 weeks | 
| metabolic parameters waist | waist circumference (cm) | 12 weeks | 
| metabolic parameters SMBG | SMBG self monitored blood glucose (mmol/l) 7 points profile in diary | 12 weeks | 
| metabolic parameters quality of life | Quality of life questionnaire | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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beta cell