GABA Treatment in Subjects With Type 1 Diabetes (GABA-1)

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

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

Study Overview

• Status: Unknown
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Dietary supplement: Gama amino butyric acid (GABA); Dietary supplement: placebo

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 Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Peter Rossing, MD; Phone Number: 004530913383; Email: peter.rossing@regionh.dk

Study Locations

• Denmark
  • Gentofte, Denmark, 2820
    • Recruiting
    • Steno Diabetes Center Copenhagen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:stimulated c peptide <0.03 mmol/l type 1 diabetes

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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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Steno Diabetes Center Copenhagen
• Collaborators: Juvenile Diabetes Research Foundation
• Investigators: Study Chair: peter Rossing, md, Steno Diabetes Center Copenhagen

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2018
• Primary Completion (Anticipated): May 1, 2019
• Study Completion (Anticipated): July 1, 2019

Study Registration Dates

• First Submitted: October 22, 2018
• First Submitted That Met QC Criteria: October 25, 2018
• First Posted (Actual): October 26, 2018

Study Record Updates

• Last Update Posted (Actual): October 26, 2018
• Last Update Submitted That Met QC Criteria: October 25, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: beta cell
• 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; Histamine Antagonists; Histamine Agents; Butyric Acid
• Other Study ID Numbers: H17041847

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: data protection rules may not approve data sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No