Pharmacokinetics Study of Gamma-aminobutyric Acid
Condition: Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1; Metabolic Diseases; Glucose Metabolism Disorders; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases
Study type: Observational

Summary: 
      The purpose of this study is to determine upon administering GABA orally to a person how it
      is absorbed, distributed, as well as the drug's pharmacological effects on the body such as
      glucose levels, serum C-peptide and/or insulin levels (referred to as
      pharmacokinetics/pharmacodynamics). We will conduct experiments in normal subjects to address
      these questions.
    

Detailed description: 
      Type 1 diabetes is an autoimmune disease resulting from the progressive loss of pancreatic
      insulin-secreting beta-cells. This consequently leads to a lack of insulin and elevation of
      blood sugar, namely hyperglycemia, which is a major cause for the development of diabetes and
      its acute or chronic complications. The current treatment for type 1 diabetes requires a
      life-long dependency on daily insulin injections, causing inconvenience and burden to
      patients. Drug-induced hypoglycemia is also common as it presents a major challenge in
      insulin therapy. Furthermore, although insulin therapy is lifesaving, it is not a cure as it
      neither reverses the progression of the disease nor prevents the development of serious
      complications associated with this disease. New treatments are urgently needed.

      Recent studies have demonstrated that a natural chemical found in the brain,
      gamma-aminobutyric acid (GABA), which is also produced in large quantities by pancreatic
      beta-cells, has beta-cell regenerative and immunoregulatory effects. Importantly, GABA
      prevented and partially reversed diabetes in type 1 diabetes mouse models. It is important to
      address essential questions regarding the potential effects of GABA in diabetic patients in
      humans. Given the largely unknown mechanism of action of GABA in the pancreas, and the
      limited information on how GABA is absorbed, distributed and eliminated from the human body,
      we plan to examine these issues (referred to as pharmacokinetics/pharmacodynamics) in normal
      subjects.

      The outcome of this study will provide useful information on the mechanism of action of GABA
      in human subjects.
    

Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Residents of Shanghai
      
Biospecimen description: 
      This is an open-labeled, 3-phase, self-control study. In phase 1, blood is sampled from
      volunteers who will take placebo to obtain the baseline value. In phase 2, volunteers will
      take a single oral dose of 2000 mg GABA. There are at least 7 days between the two phases. In
      phase 3, volunteers will take a repeated oral dose of 2000 mg GABA (thrice daily for seven
      days). There are at least 5-7 days between phase 3 and phase 3. In each phase, individuals
      will be observed for 24 hours to obtain the complete concentration time curve. 4 ml of blood
      will be sampled at the following time-point for predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4,
      6, 8, 10, 12 and 24 hour postdose.
    
Keywords: Gamma-aminobutyric acid; Pharmacokinetics; Pharmacodynamics; Insulin; C-peptide; Glucagon