Clinical trial NCT03721991: GABA Treatment in Subjects With Type 1 Diabetes
Official title: A Randomised, Double-blind, Placebo-controlled, Parallel Group, Single-centre Trial of GABA Treatment in Subjects With Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Type 1 Diabetes Mellitus
Keywords: beta cell
Lead sponsor: Steno Diabetes Center Copenhagen
Sponsor class: OTHER
Collaborators: name: Juvenile Diabetes Research Foundation
First posted: 2018-10-26
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomised controlled study with active compared to placebo for 12 weeks
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: insulin production
timeFrame: 12 weeks
Secondary outcomes:
measure: c peptide response (change from fasting baseline to meal stimulated concentration in blood)
timeFrame: after 12 weeks
measure: c peptide response beta cell
timeFrame: after 12 weeks
measure: glucagon response
timeFrame: after 12 weeks
measure: metabolic parameters
timeFrame: 12 weeks
measure: metabolic parameters dose of insulin
timeFrame: 12 weeks
measure: metabolic parameters glucose
timeFrame: 12 weeks
measure: metabolic parameters lipid
timeFrame: 12 weeks
measure: metabolic parameters weight
timeFrame: 12 weeks
measure: metabolic parameters waist
timeFrame: 12 weeks
measure: metabolic parameters SMBG
timeFrame: 12 weeks
measure: metabolic parameters quality of life
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Gentofte
country: Denmark
facility: Steno Diabetes Center Copenhagen
Study officials:
affiliation: Steno Diabetes Center Copenhagen
name: peter Rossing, md
role: STUDY_CHAIR
References: