Pharmacokinetics Study of Gamma-aminobutyric Acid (GABA-PK)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2013 by Huashan Hospital
Sponsor:
Collaborators:
St. Michael's Hospital, Toronto
University of Florida
University of Massachusetts, Worcester
Information provided by (Responsible Party):
Zhaoyun Zhang, Huashan Hospital
ClinicalTrials.gov Identifier:
NCT01917760
First received: July 6, 2013
Last updated: August 5, 2013
Last verified: August 2013
  Purpose

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.


Condition Phase
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Phase 1

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: The Pharmacokinetics of Gamma-aminobutyric Acid in Healthy Volunteers.

Resource links provided by NLM:


Further study details as provided by Huashan Hospital:

Primary Outcome Measures:
  • pharmacokinetic characteristics of γ-aminobutyric acid (GABA) [ Time Frame: baseline and up to 30 days ] [ Designated as safety issue: No ]

    The primary endpoint of this study is to obtain the pharmacokinetic characteristics of γ-aminobutyric acid (GABA), including:

    1. Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUC0-t),
    2. Area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUC0-∞),
    3. Maximum observed plasma concentration (Cmax),
    4. Time to maximum plasma concentration (Tmax), and
    5. Terminal elimination half-life in plasma (t½)


Secondary Outcome Measures:
  • serological characteristics [ Time Frame: baseline and up to 30 days ] [ Designated as safety issue: No ]
    plasma glucose levels, insulin, C-peptide and glucagon levels will be measured


Other Outcome Measures:
  • Exploratory measures [ Time Frame: baseline and up to 30 days ] [ Designated as safety issue: No ]
    plasma glucagon-like peptide-1 (GLP-1) and glycated serum protein (GSP)will be measured.


Biospecimen Retention:   Samples Without DNA

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.


Estimated Enrollment: 12
Study Start Date: July 2013
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
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

Ages Eligible for Study:   19 Years to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population

Residents of Shanghai

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01917760

Locations
China, Shanghai
Department of Endocrinology and Metabolism,Huashan hospital Recruiting
Shanghai, Shanghai, China, 200040
Contact: Zhaoyun Zhang, MD, PhD    021- 5288-8286    zhaoyunzhang@fudan.edu.cn   
Contact: Yi Wang, MD, PhD    021- 5288-7022    aries.520@163.com   
Principal Investigator: Yiming Li         
Principal Investigator: Qinghua Wang         
Principal Investigator: Zhen Jiao         
Sponsors and Collaborators
Huashan Hospital
St. Michael's Hospital, Toronto
University of Florida
University of Massachusetts, Worcester
Investigators
Principal Investigator: Yiming Li Huashan Hospital
Principal Investigator: Qinghua Wang Huashan Hospital/St Michael's Hospital
Principal Investigator: Zheng Jiao Huashan Hospital
  More Information

No publications provided

Responsible Party: Zhaoyun Zhang, professor of endocrinology and metabolism, Huashan Hospital
ClinicalTrials.gov Identifier: NCT01917760     History of Changes
Other Study ID Numbers: KY-2013-222, JDRF_17-2013-499
Study First Received: July 6, 2013
Last Updated: August 5, 2013
Health Authority: China: Food and Drug Administration

Keywords provided by Huashan Hospital:
Gamma-aminobutyric acid
Pharmacokinetics
Pharmacodynamics
Insulin
C-peptide
Glucagon

Additional relevant MeSH terms:
Autoimmune Diseases
Diabetes Mellitus
Diabetes Mellitus, Type 1
Endocrine System Diseases
Glucose Metabolism Disorders
Immune System Diseases
Metabolic Diseases
Gamma-Aminobutyric Acid
GABA Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 20, 2014