GABA Treatment in Subjects With Type 1 Diabetes

Not Applicable

• Conditions: Type 1 Diabetes Mellitus
• Interventions: Dietary Supplement: Gama amino butyric acid (GABA); Dietary Supplement: placebo

• Registration Number: NCT03721991
• Lead Sponsor: Steno Diabetes Center Copenhagen

Brief Summary

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

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.

Study Timeline

• Status Verified: 2018-10
• Study Start: 2018-10-10
• Study First Submitted: 2018-10-22
• Study First Submitted QC: 2018-10-25
• Last Update Submitted: 2018-10-25
• Study First Posted: 2018-10-26
• Last Update Posted: 2018-10-26
• Primary Completion: 2019-05-01
• Study Completion: 2019-07-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
GABA	Gama amino butyric acid (GABA)	gamma Amino butyric acid (GABA) food supplement with 6 g per day
PLACEBO	placebo	Matching placebo capsules to GABA

Primary Outcome Measures

Name	Time	Method
insulin production	12 weeks	c peptide production during meal stimulation

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Steno Diabetes Center Copenhagen; 🇩🇰 Gentofte, Denmark