Diabetes Mellitus
Conditions
Keywords
Diabetes Mellitus, Propionate
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.
Interventions
DIETARY_SUPPLEMENTSodium propionate
Sodium propionate capsule or tablet
DIETARY_SUPPLEMENTSodium Chloride
Placebo capsule or tablet
PROCEDUREOral glucose tolerance test
PROCEDUREIntravenous glucose tolerance test.
Sponsors
Imperial College London
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
the study was terminated so data were referred to only 6 people despite a target recruitment of 12
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
Countries
United Kingdom
Participant flow
Recruitment details
Recruitment started March 2013 and ended August 2016. The study was based at the clinical research facility at Imperial College Health Care Trust but never completed. Only 6 where recriuted and completed. The target was 12
Pre-assignment details
Wash out of 7 days between interventions
Participants by arm
| Arm | Count |
|---|---|
| Sodium Chloride Sodium Chloride Pill Intervention | 3 |
| Sodium Propionate Sodium propionate pill | 3 |
| Total | 6 |
Baseline characteristics
| Characteristic | Sodium Chloride | Sodium Propionate | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 3 Participants | 6 Participants |
| Propionate | 0.05 micromol/l STANDARD_DEVIATION 0.05 | 0.05 micromol/l STANDARD_DEVIATION 0.05 | 0.05 micromol/l STANDARD_DEVIATION 0.05 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 3 Participants | 6 Participants |
| Region of Enrollment United Kingdom | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 |
| other Total, other adverse events | 0 / 3 | 0 / 3 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 |
Outcome results
Primary
Propionate CMax
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)
Time frame: hours (up to 8hrs)
Population: Propionate concertation in plasma
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sodium Chloride Capsule | Propionate CMax | 7.2 mmol/l | Standard Deviation 0.26 |
| Sodium Propionate Capsule | Propionate CMax | 7.79 mmol/l | Standard Deviation 0.25 |
Secondary
Insulin Levels in Response to the Absorption of Proprionate (Total Insulin Across All Time Points)
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)
Time frame: hours (up to 8 hours)
Population: The mean below was estimated first per patient (across all the above time points) and then per arm across the 6 patients.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Sodium Chloride Capsule | Insulin Levels in Response to the Absorption of Proprionate (Total Insulin Across All Time Points) | 8142 uM/l |
| Sodium Propionate Capsule | Insulin Levels in Response to the Absorption of Proprionate (Total Insulin Across All Time Points) | 8316 uM/l |
Secondary
Insulinogenic Index (Change in Insulin Divided by the Change in Glucose Over the First 30 Minutes of the Test)
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)
Time frame: 30mins
Population: This index is estimated on a scale 0 to 50 where 0 is the lowest value and 50 is the highest value
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sodium Chloride Capsule | Insulinogenic Index (Change in Insulin Divided by the Change in Glucose Over the First 30 Minutes of the Test) | 30.2 index | Standard Deviation 12 |
| Sodium Propionate Capsule | Insulinogenic Index (Change in Insulin Divided by the Change in Glucose Over the First 30 Minutes of the Test) | 31 index | Standard Deviation 12.5 |
Secondary
Total Amount of Insulin Stimulated by Propionate Per Unit Time (Incremental Area Under the Curve)
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
Time frame: 10 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sodium Chloride Capsule | Total Amount of Insulin Stimulated by Propionate Per Unit Time (Incremental Area Under the Curve) | 677.5 uM/min | Standard Error 24 |
| Sodium Propionate Capsule | Total Amount of Insulin Stimulated by Propionate Per Unit Time (Incremental Area Under the Curve) | 678 uM/min | Standard Error 25 |