Oral Propionate to Treat and Prevent Diabetes

Development of Orally Administered Sodium Propionate to Treat and Prevent Diabetes

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

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus
• Intervention / Treatment: Dietary supplement: Sodium Chloride; Procedure: Oral glucose tolerance test; Procedure: Intravenous glucose tolerance test.; Dietary supplement: Sodium propionate

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 Type: Interventional
• Enrollment (Actual): 90
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W12 0NN
    • Imperial College London
  • London, United Kingdom, W12 0NN
    • St John McMichael Centre - Imperial College London
  • UK
    • London, UK, United Kingdom, W12 0NN
      • Hammersmith Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Sodium chloride pill; Study 1: pharmacokinetics Study2: Oral glucose tolerance test Study 3: intravenous glucose tolerance test	Dietary supplement: Sodium Chloride; Placebo capsule or tablet; Procedure: Oral glucose tolerance test; Procedure: Intravenous glucose tolerance test.
Experimental: Sodium propionate pill; Study 1: pharmacokinetics Study2: Oral glucose tolerance test Study 3: intravenous glucose tolerance test	Procedure: Oral glucose tolerance test; Procedure: Intravenous glucose tolerance test.; Dietary supplement: Sodium propionate; Sodium propionate capsule or tablet

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin	Plasma insulin	-10, 0, 15, 30, 60, 90, 120, 150, 180, 4h, 6h, 8h

Collaborators and Investigators

• Sponsor: Imperial College London
• Investigators: Principal Investigator: Gavin A Bewick, PhD., Imperial College London

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2013
• Primary Completion (Actual): August 1, 2019
• Study Completion (Actual): August 1, 2019

Study Registration Dates

• First Submitted: September 11, 2012
• First Submitted That Met QC Criteria: September 20, 2012
• First Posted (Estimate): September 25, 2012

Study Record Updates

• Last Update Posted (Actual): October 15, 2019
• Last Update Submitted That Met QC Criteria: October 14, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Diabetes Mellitus; Propionate
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus
• Other Study ID Numbers: CRO2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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