Clinical trial NCT01692002: Oral Propionate to Treat and Prevent Diabetes
Official title: Development of Orally Administered Sodium Propionate to Treat and Prevent Diabetes
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Diabetes Mellitus
Keywords: Diabetes Mellitus
Propionate
Lead sponsor: Imperial College London
Sponsor class: OTHER
First posted: 2012-09-25
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: the study was terminated so data were referred to only 6 people despite a target recruitment of 12
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Propionate CMax
timeFrame: hours (up to 8hrs)
Secondary outcomes:
measure: Total Amount of Insulin Stimulated by Propionate Per Unit Time (Incremental Area Under the Curve)
timeFrame: 10 minutes
measure: Insulinogenic Index (Change in Insulin Divided by the Change in Glucose Over the First 30 Minutes of the Test)
timeFrame: 30mins
measure: Insulin Levels in Response to the Absorption of Proprionate (Total Insulin Across All Time Points)
timeFrame: hours (up to 8 hours)
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Hammersmith Hospital
state: UK
city: London
country: United Kingdom
facility: Imperial College London
city: London
country: United Kingdom
facility: St John McMichael Centre - Imperial College London
Study officials:
affiliation: Imperial College London
name: Gavin A Bewick, PhD.
role: PRINCIPAL_INVESTIGATOR
References: