Oral Propionate to Treat and Prevent Diabetes

Not Applicable

Terminated

• Conditions: Diabetes Mellitus

• 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.

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
• Results First Submitted: 2022-11-15
• Status Verified: 2025-06
• Results First Submitted QC: 2025-06-02
• Last Update Submitted: 2025-06-02
• Results First Posted: 2025-06-18
• Last Update Posted: 2025-06-18

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 6

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%,

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Primary Outcome Measures

Name	Time	Method
Propionate CMax	hours (up to 8hrs)	Study 1: Peak plasma concentration of propionate. Dose ranging and pharmacokinetic profile of propionate by Mass spectrometry has been measured at -10, 0, 15, 30, 60, 90, 120, 150, 180, 4h, 6h, 8h (the mean below was estimated first per patient (across all the above time points) and then per arm across the 6 patients)

Secondary Outcome Measures

Name	Time	Method
Total Amount of Insulin Stimulated by Propionate Per Unit Time (Incremental Area Under the Curve)	10 minutes	Study 3: Participants will undergo a frequently sampled oral glucose tolerance test (OGTT) to detect changes in insulin sensitivity and beta cell function. Where maximum insulin increments during a glucose tolerance test will be reported on a scale 0 to 1000 where 0 is the lowest and 1000 is the highest outcome
Insulinogenic Index (Change in Insulin Divided by the Change in Glucose Over the First 30 Minutes of the Test)	30mins	Study 2: insulinogenic index. Oral glucose tolerance dose finding was measured with commercially available kits (the mean below was estimated per arm across the 6 patients)
Insulin Levels in Response to the Absorption of Proprionate (Total Insulin Across All Time Points)	hours (up to 8 hours)	Plasma insulin has been measured using commercially available kits at -10, 0, 15, 30, 60, 90, 120, 150, 180, 4h, 6h, 8h (the mean below was estimated first per patient (across all the above time points) and then per arm across the 6 patients)

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