Oral Propionate to Treat and Prevent Diabetes

Study Overview
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Brief Summary
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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
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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.

Official Title
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Development of Orally Administered Sodium Propionate to Treat and Prevent Diabetes

Conditions
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Diabetes Mellitus

Intervention / Treatment
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* Dietary Supplement: Sodium propionate
* Dietary Supplement: Sodium Chloride
* Procedure: Oral glucose tolerance test
* Procedure: Intravenous glucose tolerance test.


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Sodium chloride pill<br>Study 1: pharmacokinetics Study2: Oral glucose tolerance test Study 3: intravenous glucose tolerance test | Dietary Supplement: Sodium Chloride<br>* Placebo capsule or tablet<br>Procedure: Oral glucose tolerance test<br> <br> Procedure: Intravenous glucose tolerance test.<br> <br> |
| Experimental: Sodium propionate pill<br>Study 1: pharmacokinetics Study2: Oral glucose tolerance test Study 3: intravenous glucose tolerance test | Dietary Supplement: Sodium propionate<br>* Sodium propionate capsule or tablet<br>Procedure: Oral glucose tolerance test<br> <br> Procedure: Intravenous glucose tolerance test.<br> <br> |

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes Mellitus, Propionate