Obesity
Conditions
Keywords
Obesity, Short chain fatty acids, Appetite, Body weight, Insulin sensitivity, Propionate, Propionate ester
Brief summary
This study explores the nutritional effects of fibre. Short chain fatty acid(SCFA), such as propionate, are produced through the fermentation of fibre in the bowel. SCFA are thought to have direct beneficial effects on the gut, appetite, weight and fat distribution. This study will look into these effects by conducting a dose finding study and then a randomised controlled study using healthy human volunteers.
Detailed description
This is a dose finding study in healthy overweight to obese human volunteers (BMI 25- 35) to find the level of oral supplementation with propionate that increases plasma propionate levels to 10x the current normal plasma level and use this dose of propionate in a randomised, placebo controlled double bind study. This study will compare propionate with fermentable and non fermentable carbohydrate. The outcome measures for this study will include assessments of appetite with feeding studies, measurement of insulin sensitivity using hyperinsulinaemic euglycaemic clamps and assessment of adipose tissue distribution using MRI scans and adipose tissue biopsy to determine changes in proliferation and differentiation of adipocytes.
Interventions
DIETARY_SUPPLEMENTPropionate ester
The subject will take propionate ester at the dose specified by the dose finding study, three times a day for 24 weeks
DIETARY_SUPPLEMENTInulin
The subjects in this group will take inulin at a comparable dose, three times a day for 24 weeks
DIETARY_SUPPLEMENTCellulose
The subjects in this group will take the non fermentable carbohydrate, cellulose, at a comparable dose for 24 weeks.
Sponsors
Imperial College London
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male and female volunteers aged between 21 and 65 years
Exclusion criteria
* Weight change of more than 3kg in the preceding 2 months * Current smokers * Substance abuse * Excess alcohol intake * Pregnancy * Diabetes * Cardiovascular disease * Cancer * Gastrointestinal disease e.g. inflammatory bowel disease or irritable bowel syndrome * Kidney disease * Liver disease * Pancreatitis * Use of medications including: anti inflammatory drugs or steroids, cholesterol lowering medication, androgens, phenytoin, erythromycin or thyroid hormones.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Appetite_Food Intake | Baseline, 24 weeks | The change in food intake following 24 weeks of supplementation |
| Body Weight | Baseline, 24 weeks | Body weight was measured in all subjects to the nearest 0.1 kg (Tanita BC-418MA) while subjects were wearing light clothing. |
| Body Weight - Number of Participants Gained ≥3% of Their Baseline Body Weight | Baseline, 24 weeks | Body weight was measured in all subjects to the nearest 0.1 kg (Tanita BC-418MA) while subjects were wearing light clothing. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adipose Tissue Distribution - Intra-abdominal Adipose Tissue | 24 weeks | Body composition was assessed using MRI and MR spectroscopy (MRS), expressed as a percentage of total adipose tissue content. |
| Insulin Sensitivity - HOMA IR | 24 weeks | The homeostatic model assessment (HOMA) is a method used to quantify insulin resistance and beta-cell function. |
Countries
United Kingdom
Participant flow
Pre-assignment details
Non fermentable arm not conducted
Participants by arm
| Arm | Count |
|---|---|
| Inulin-control Participants received inulin | 24 |
| Inulin-propionate Ester Participants received inulin-propionate ester | 25 |
| Total | 49 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 2 | 2 |
| Overall Study | Protocol Violation | 4 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Inulin-control | Inulin-propionate Ester | 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 | 24 Participants | 25 Participants | 49 Participants |
| Age, Continuous | 53.4 years STANDARD_DEVIATION 1.5 | 55.3 years STANDARD_DEVIATION 1.4 | 54 years STANDARD_DEVIATION 1.4 |
| HbA1c | 37.8 mmol/mol STANDARD_DEVIATION 0.5 | 38.2 mmol/mol STANDARD_DEVIATION 0.7 | 38 mmol/mol STANDARD_DEVIATION 0.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 5 Participants | 9 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 4 Participants | 6 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 | 18 Participants | 16 Participants | 34 Participants |
| Region of Enrollment United Kingdom | 24 participants | 25 participants | 49 participants |
| Sex: Female, Male Female | 15 Participants | 15 Participants | 30 Participants |
| Sex: Female, Male Male | 9 Participants | 10 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 31 | 0 / 29 |
| other Total, other adverse events | 14 / 31 | 5 / 29 |
| serious Total, serious adverse events | 0 / 31 | 0 / 29 |
Outcome results
Primary
Appetite_Food Intake
The change in food intake following 24 weeks of supplementation
Time frame: Baseline, 24 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Inulin-control | Appetite_Food Intake | Baseline | 678 kcal |
| Inulin-control | Appetite_Food Intake | 24 weeks | 645 kcal |
| Inulin-propionate Ester | Appetite_Food Intake | Baseline | 836 kcal |
| Inulin-propionate Ester | Appetite_Food Intake | 24 weeks | 763 kcal |
p-value: 0.972Regression, Linear
Primary
Body Weight
Body weight was measured in all subjects to the nearest 0.1 kg (Tanita BC-418MA) while subjects were wearing light clothing.
Time frame: Baseline, 24 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inulin-control | Body Weight | Baseline | 91 kg | Standard Error 2.8 |
| Inulin-control | Body Weight | 24 weeks | 91.4 kg | Standard Error 3 |
| Inulin-propionate Ester | Body Weight | Baseline | 88.5 kg | Standard Error 2.9 |
| Inulin-propionate Ester | Body Weight | 24 weeks | 87.5 kg | Standard Error 3 |
Comparison: Baseline and 24 weeksp-value: 0.559t-test, 2 sided
Comparison: Baseline to 24 weeksp-value: 0.062t-test, 2 sided
p-value: 0.099Regression, Linear
Primary
Body Weight - Number of Participants Gained ≥3% of Their Baseline Body Weight
Body weight was measured in all subjects to the nearest 0.1 kg (Tanita BC-418MA) while subjects were wearing light clothing.
Time frame: Baseline, 24 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Inulin-control | Body Weight - Number of Participants Gained ≥3% of Their Baseline Body Weight | 6 Participants |
| Inulin-propionate Ester | Body Weight - Number of Participants Gained ≥3% of Their Baseline Body Weight | 1 Participants |
p-value: 0.036Regression, Linear
Secondary
Adipose Tissue Distribution - Intra-abdominal Adipose Tissue
Body composition was assessed using MRI and MR spectroscopy (MRS), expressed as a percentage of total adipose tissue content.
Time frame: 24 weeks
Population: MRS data could not be collected in 17 subjects, due to metal implants (n=8) and claustrophobia (n=9).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inulin-control | Adipose Tissue Distribution - Intra-abdominal Adipose Tissue | Baseline | 10.6 percentage of total adipose tissue | Standard Error 1.3 |
| Inulin-control | Adipose Tissue Distribution - Intra-abdominal Adipose Tissue | 24 weeks | 11.1 percentage of total adipose tissue | Standard Error 1.4 |
| Inulin-propionate Ester | Adipose Tissue Distribution - Intra-abdominal Adipose Tissue | Baseline | 13.2 percentage of total adipose tissue | Standard Error 1.2 |
| Inulin-propionate Ester | Adipose Tissue Distribution - Intra-abdominal Adipose Tissue | 24 weeks | 13.1 percentage of total adipose tissue | Standard Error 1.1 |
Comparison: Baseline to 24 weeksp-value: 0.001t-test, 2 sided
Comparison: Baseline to 24 weeksp-value: 0.723t-test, 2 sided
p-value: 0.027Regression, Linear
Secondary
Insulin Sensitivity - HOMA IR
The homeostatic model assessment (HOMA) is a method used to quantify insulin resistance and beta-cell function.
Time frame: 24 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inulin-control | Insulin Sensitivity - HOMA IR | Baseline | 2.7 percentage of Beta Cell Function | Standard Deviation 0.3 |
| Inulin-control | Insulin Sensitivity - HOMA IR | 24 weeks | 2.3 percentage of Beta Cell Function | Standard Deviation 0.2 |
| Inulin-propionate Ester | Insulin Sensitivity - HOMA IR | Baseline | 2 percentage of Beta Cell Function | Standard Deviation 0.2 |
| Inulin-propionate Ester | Insulin Sensitivity - HOMA IR | 24 weeks | 2 percentage of Beta Cell Function | Standard Deviation 0.2 |
p-value: 0.372t-test, 2 sided
p-value: 0.644t-test, 2 sided
p-value: 0.549Regression, Linear