Clinical trial NCT01917760: Pharmacokinetics Study of Gamma-aminobutyric Acid
Official title: The Pharmacokinetics of Gamma-aminobutyric Acid in Healthy Volunteers.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Keywords: Gamma-aminobutyric acid
Pharmacokinetics
Pharmacodynamics
Insulin
C-peptide
Glucagon
Lead sponsor: Huashan Hospital
Sponsor class: OTHER
Collaborators: name: Unity Health Toronto
name: University of Florida
name: University of Massachusetts, Worcester
First posted: 2013-08-07
Enrollment: 12
Sex: ALL
Minimum age (years): 19
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Residents of Shanghai

Brief 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.

Eligibility criteria: Inclusion Criteria:

1. Volunteers in good health condition between 19 and 40 years of age (inclusive) at the time of signing the informed consent.
2. Body mass index (BMI) between 18.5 and 24 kg/m2 (inclusive), with weight greater than 50 kg.
3. Not on any medication 2 weeks before screening.
4. No blood donation within 3 months before screening.
5. Must sign the informed consent. Note: Blood and biochemical tests must be normal during the screening. However, if the participant's test-results were beyond the normal range, the individual can still be recruited as long as the results do not affect the experiment.

Exclusion Criteria:

1. Abnormalities of physical examination, laboratory tests, or ECG in screening, which may influence the results of the study.
2. Previous or existing history of severe heart, liver, kidney, gastrointestinal, nervous system, mental, or metabolic abnormalities as well as other diseases which can affect drug absorption, circulation, metabolism, or excretion.
3. History of alcoholism, smoking, or drug abuse within the past 1 year.
4. Participation in any clinical drug study within the past 30 days.
5. Any definite or suspected allergy or family history of allergy to GABA or any other similar drugs.

Primary outcomes:
measure: pharmacokinetic characteristics of γ-aminobutyric acid (GABA)
timeFrame: baseline and up to 30 days
Secondary outcomes:
measure: serological characteristics
timeFrame: baseline and up to 30 days
Other outcomes:
measure: Exploratory measures
timeFrame: baseline and up to 30 days
Locations:
city: Shanghai
country: China
facility: Department of Endocrinology and Metabolism，Huashan hospital
state: Shanghai
Study officials:
affiliation: Huashan Hospital
name: Yiming Li
role: PRINCIPAL_INVESTIGATOR
affiliation: Huashan Hospital/St Michael's Hospital
name: Qinghua Wang
role: PRINCIPAL_INVESTIGATOR
affiliation: Huashan Hospital
name: Zheng Jiao
role: PRINCIPAL_INVESTIGATOR
References: