Intervention With a GABA Supplement in Prediabetics

The Effects of a GABA Supplement Versus a Placebo on Glucose Tolerance and Blood Pressure in Prediabetics

In this double-blind parallel placebo controlled intervention study the effects of 3 times daily 500 mg gamma-aminobutyric acid (GABA) supplementation on glucose tolerance and cardiovascular health will be assessed in prediabetics.

Study Overview

• Status: Completed
• Conditions: Hypertension; Prediabetes
• Intervention / Treatment: Dietary supplement: GABA; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Wageningen, Netherlands
    • Wageningen University, Division of Human Nutrition

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 48 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age between 50 and 70
• BMI higher or equal to 27 kg/m2
• Impaired fasting glucose (fasting glucose ≥ 6.1 and ≤ 6.9 mmol/L) or/and
• Impaired glucose tolerance (glucose levels ≥ 7.8 and ≤ 11.1 mmol/L, 2-hours after an OGTT or/and glucose levels ≥8.6 mmol/L, 1-hour after an OGTT)

Exclusion Criteria:

• Has been diagnosed with diabetes
• Having other conditions, like liver, pancreatic, cardiovascular, gastro-intestinal or endocrine diseases, that could influence the study results
• Use of medications or supplements that could influence the study results
• Sensitive to medical skin adhesives
• More than 5kg weight change in the past 12 weeks
• Excessive alcohol consumption (>21 glasses/week for men and >14 glasses/week for women on average)
• Being an employee of Wageningen University, division Human Nutrition and Health
• Currently a research subject in other research

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GABA; GABA is a nutrient commonly present in our diet in for example tomatoes and potatoes. It is also commercially sold as dietary supplement. A dose of 500 mg, 3 times daily is used	Dietary supplement: GABA; The dietary supplement GABA will be taken orally 3 times daily, before each main meal
Placebo Comparator: Placebo; The placebo consists of capsules containing powdered cellulose.	Other: Placebo; Gelatin capsule containing powdered cellulose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postprandial glycaemic response during a 2 hour oral glucose tolerance test (OGTT)	A 2 hour oral glucose tolerance test with 75gr glucose	blood will be drawn at baseline and after 30, 60 and 120 minutes, before and after the 12 weeks intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postprandial insulin and glucagon response during a 2 hour OGTT,	A 2 hour oral glucose tolerance test with 75gr glucose	blood will be drawn at baseline and after 30, 60 and 120 minutes, before and after the 12 weeks intervention
Plasma free fatty acids		before and after the 12 weeks intervention
HbA1c		before and after the 12 weeks intervention
Glucose variability	The participants wear a flash glucose monitoring sensor with which their interstitial glucose is measured every 15 minutes.	5 days during which they eat their habitual diet, before and after the 12 weeks intervention
Blood pressure	Single measurement and a dynamic measurement: Mean day systolic and diastolic blood pressure; Mean night systolic and diastolic blood pressure; Time below or above 120/80 mmHg	Dynamic measurement: 24 hours, before and after the 12 weeks intervention
Heart rate		before and after the 12 weeks intervention
Concentrion of markers of inflammation in blood	C-reactive protein and cytokines like IL-6 and TNF-alpha	before and after the 12 weeks intervention
Concentration of triglycerides in blood		before and after the 12 weeks intervention
Concentration of LDL and HDL cholesterol in blood		before and after the 12 weeks intervention
Concentration of ALAT and ASAT in blood		before and after the 12 weeks intervention
Acute effects of GABA on postprandial glucose	Assessed with an OGTT during which interstitial glucose is measured with flash glucose monitoring	2 hours, after a single administration of 500 mg GABA
Acute effects of GABA on blood pressure	Assessed with an ambulatory blood pressure monitor	for 24 hours during which GABA is taken 3 times, each time before the main meal
Sleep quality	Pittsburgh Sleep Quality Index (PSQI) questionnaire, the outcome is a global PSQI score (range: 0-21), with higher scores indicating poorer sleep quality.	before and after the 12 weeks intervention
Feelings of depression	Patient Health Questionnaire (PHQ-9), the higher the score the more depressed a person is.	before and after the 12 weeks intervention
Feelings of anxiety	General Anxiety Disorder (GAD-7) questionnaire, the higher the score, the more anxious a person is.	before and after the 12 weeks intervention
Plasma GABA concentration		before and after the 12 weeks intervention
Plasma glutamate concentration		before and after the 12 weeks intervention

Collaborators and Investigators

• Sponsor: Wageningen University
• Collaborators: Nunhems; Agrico Research; Avebe
• Investigators: Principal Investigator: Renger Witkamp, PhD, Wageningen University

Publications and helpful links

General Publications

• de Bie TH, Balvers MGJ, de Vos RCH, Witkamp RF, Jongsma MA. The influence of a tomato food matrix on the bioavailability and plasma kinetics of oral gamma-aminobutyric acid (GABA) and its precursor glutamate in healthy men. Food Funct. 2022 Aug 15;13(16):8399-8410. doi: 10.1039/d2fo01358d.

Study record dates

Study Major Dates

• Study Start (Actual): September 29, 2020
• Primary Completion (Actual): September 8, 2021
• Study Completion (Actual): September 8, 2021

Study Registration Dates

• First Submitted: March 4, 2020
• First Submitted That Met QC Criteria: March 4, 2020
• First Posted (Actual): March 11, 2020

Study Record Updates

• Last Update Posted (Actual): November 16, 2021
• Last Update Submitted That Met QC Criteria: November 15, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Prediabetic State
• Other Study ID Numbers: NL73194.081.20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No