Oral Propionate to Treat and Prevent Diabetes

Not Applicable

Completed

• Conditions: Diabetes Mellitus
• Interventions: Dietary Supplement: Sodium propionate; Dietary Supplement: Sodium Chloride; Procedure: Oral glucose tolerance test; Procedure: Intravenous glucose tolerance test.

• Registration Number: NCT01692002
• Lead Sponsor: Imperial College London

Brief Summary

The aim of these studies is to firstly determine the pharmacokinetic profile of orally administered enteric coated sodium propionate. Subsequently, the most efficacious dose at improving glucose tolerance following an oral glucose challenge will be determined. The investigators will then determine the mechanism of action of propionate, whether it acts by altering beta cell function directly or by augmenting the incretin effect or both

Detailed Description

The NHS spends £1M per hour, 10% of its yearly budget, treating diabetes. In the UK cases of diabetes are expected to top 4 million by 2025. There is an urgent need for new therapies. The short chain fatty acid propionate is a natural substance produced by digestion of fermentable carbohydrates. Preclinical and early human data demonstrate it improves pancreatic function and glucose control. The investigators aim to conduct proof of principle studies to determine if oral delivery of propionate improves glucose control in patients at risk of developing diabetes.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2012-09-11
• Study First Submitted QC: 2012-09-20
• Study First Posted: 2012-09-25
• Study Start: 2013-01
• Primary Completion: 2019-08
• Study Completion: 2019-08
• Status Verified: 2019-10
• Last Update Submitted: 2019-10-14
• Last Update Posted: 2019-10-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

Study 1: Healthy men and women aged between 18 and 70 years with BMI between 20-25 kg/m2 and with normal fasting blood glucose (below5.5mmol/l and HbA1C less than 5.7% will be eligible to volunteer.

Study 2: As for Study 1. Study 3: Cohort 1: Volunteers aged between 30 to 70 with a BMI between 25-35 kg/m2 who do not have impaired fasting glucose and have HbA1c below 5.7%.

Cohort 2: Volunteers aged between 30 to 70 years with a BMI between 25-35 kg/m2 who have impaired fasting glucose (between 5.5-7mmol/l) and HbA1C between 5.7% and 6.5%,

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Exclusion Criteria

• Type 1 or Type 2 Diabetes

• Gained or lost ≥ 3kg weight in the past three months
• Taken prescription medicines having an impact on metabolism, appetite regulation, glucose homeostasis and hormonal regulation
• Taken any dietary supplements in the last 6 months
• Any chronic illness
• Cardiovascular disease
• Excess alcohol intake
• Current smokers
• Any gastrointestinal disorder e.g. Crohn's disease, coeliac disease or irritable bowel syndrome
• A history of drug or alcohol abuse in the last 2 years
• Pregnancy (all women of child bearing age will undergo a pregnancy test).
• Pancreatitis
• Use of medications likely to interfere with glucose metabolism, appetite regulation, hormonal balance.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Sodium propionate pill	Oral glucose tolerance test	Study 1: pharmacokinetics Study2: Oral glucose tolerance test Study 3: intravenous glucose tolerance test
Sodium chloride pill	Oral glucose tolerance test	Study 1: pharmacokinetics Study2: Oral glucose tolerance test Study 3: intravenous glucose tolerance test
Sodium propionate pill	Sodium propionate	Study 1: pharmacokinetics Study2: Oral glucose tolerance test Study 3: intravenous glucose tolerance test
Sodium chloride pill	Sodium Chloride	Study 1: pharmacokinetics Study2: Oral glucose tolerance test Study 3: intravenous glucose tolerance test
Sodium propionate pill	Intravenous glucose tolerance test.	Study 1: pharmacokinetics Study2: Oral glucose tolerance test Study 3: intravenous glucose tolerance test
Sodium chloride pill	Intravenous glucose tolerance test.	Study 1: pharmacokinetics Study2: Oral glucose tolerance test Study 3: intravenous glucose tolerance test

Primary Outcome Measures

Name	Time	Method
Study 1: Peak plasma concentration of propionate	at -10, 0, 15, 30, 60, 90, 120, 150, 180, 4h, 6h, 8h	Dose ranging and pharmacokinetic profile
Study 2: insulinogenic index	0-30mins	oral glucose tolerance dose finding
Study 3: Incremental area under the insulin profile	0-10mins	Intravenous glucose tolerance test

Secondary Outcome Measures

Name	Time	Method
Insulin	-10, 0, 15, 30, 60, 90, 120, 150, 180, 4h, 6h, 8h	Plasma insulin

Trial Locations

Locations (3)

Hammersmith Hospital; 🇬🇧 London, UK, United Kingdom

Imperial College London; 🇬🇧 London, United Kingdom

St John McMichael Centre - Imperial College London; 🇬🇧 London, United Kingdom