Long-term Metabolic Effects of Cafestol
- Conditions
- Obesity, Abdominal
- Interventions
- Dietary Supplement: CafestolDietary Supplement: Placebo
- Registration Number
- NCT05672433
- Lead Sponsor
- University of Aarhus
- Brief Summary
Twelve-week double-blinded, placebo-controlled, parallel intervention study on 40 participants with a large waist circumference who will ingest cafestol or placebo capsules twice daily. Insulin resistance is measured before and after the twelve-week intervention.
- Detailed Description
Participants are randomly allocated to the cafestol intervention group or placebo group. Before and after the twelve-week intervention the participants partake in:
* A modified two-stage Insulin Suppression Test to determine insulin mediated glucose uptake. Fasting participants receive body-surface-area-adjusted octreotide, insulin and glucose infusions for 240 minutes. Octreotide is infused with the same rate throughout the test. Insulin and glucose infusions are slow for the initial 120-minute stage and increased the final 120-minute stage, simulating fasting and post-postprandial conditions, respectively. Steady state measurements of plasma glucose are acquired the final 30 minutes of each stage, at time points 100, 110, 120, 220, 230 and 240 minutes.
* A mixed meal test. Fasting participants consume 75 g. white bread, 10 g. butter, 30 g. cheese and 200 ml. orange juice. Blood samples are drawn at time points -15, 0, 15, 30, 60, 90, 120, 180 and 240 min for glucose-, insulin-, glucagon- and triglyceride measurements.
* A Magnetic Resonance Imaging (MRI) scan. Participants undergo dixon-sequences scanning the abdomen, assessing visceral and sub-cutaneous fat volume and liver fat content. Magnetic Resonance (MR) spectroscopy is also used to determine fat percentage of the liver.
* 24-hour ambulatory blood pressure measurement, every 20 minutes during daytime and every 30 minutes during nighttime.
* 1-week continuous glucose measurement using blinded continuous glucose monitor/sensor on upper arm.
* Fecal and urine sampling
* 72-hour food-diary
* Fasting blood samples:
* Insulin, c-peptide, HbA1c and glucose
* Total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL) and triglycerides
* Thyroid-stimulating hormone (TSH)
* Alanine aminotransferase, creatinine, sodium and potassium
* High sensitivity C reactive protein (CRP) and alpha-hydroxybutyrate
* C-terminal telopeptide (CTX) and Procollagen type 1 N-terminal propeptide (P1NP)
* Parathyroid hormone (PTH), Vitamin D and Ionized calcium
* Monocyte Chemoattractant Protein-1 (MCP-1)
* Interleukin 1 \& 8 (IL-1α, IL-1β, IL-8)
* Gastric inhibitory polypeptide (GIP), Glucagon-like peptide-1 (GLP-1) and Glucagon- like peptide-2 (GLP-2)
* Growth/differentiation factor 15 (GDF-15)
* Tumor necrosis factor (TNFα)
* Fasting assessment of insulin resistance (Homeostatic Model Assessment for Insulin Resistance by C-peptide).
Pre-intervention and end-intervention test results will be compared using repeated-measures ANOVA / mixed models.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 40
Waist circumference > 102 cm (men) / 88 cm (women)
- Type 2 diabetes (HbA1c > 48 mmol/mol) or in treatment with antidiabetic drugs
- Pregnancy
- Planned pregnancy
- Breastfeeding
- Significant comorbidity expected to unable the subject from completing visits
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cafestol Cafestol Participants in this arm ingest 6 mg cafestol capsules twice daily with breakfast and dinner. Placebo Placebo Participants in this arm ingest placebo capsules twice daily with breakfast and dinner.
- Primary Outcome Measures
Name Time Method Steady state plasma glucose during stage 2 of insulin suppression test (mmol/L) 220, 230 and 240 minutes after test-start. Comparison between pre-intervention and end-intervention steady state plasma glucose. Subjects are administered a 25 μg octreotide bolus at time-point 0 minutes and subsequently infused with 0.27 μg octreotide / m2 • minute, 6 milliunits (mU) insulin / m2 • minute, and 50 mg glucose / m2 • minute. At time-point 120 minutes, infusion speeds were increased to to 32 mU insulin / m2 • minute and 267 mg glucose / m2 • minute.
Steady state plasma glucose during stage 1 of insulin suppression test (mmol/L) 100, 110 and 120 minutes after test-start. Comparison between pre-intervention and end-intervention steady state plasma glucose. Subjects are administered a 25 μg octreotide bolus at time-point 0 minutes and subsequently infused with 0.27 μg octreotide / m2 • minute, 6 mU insulin / m2 • minute, and 50 mg glucose / m2 • min.
Area under the curve for glucose during mixed meal test (mmol/L*min) -15 to 240 minutes from ingestion of standardized meal at time point 0 minutes. Comparison between pre-intervention and end-intervention area under the curves. Area under the curve for glucose during a mixed meal test.
- Secondary Outcome Measures
Name Time Method Area under the curve for insulin during mixed meal test (pmol/L*min) -15 to 240 minutes from ingestion of standardized meal at time point 0 minutes. Comparison between pre-intervention and end-intervention area under the curves. Area under the curve for insulin during a mixed meal test.
Area under the curve for glucagon during mixed meal test (pmol/L*min) -15 to 240 minutes from ingestion of standardized meal at time point 0 minutes. Comparison between pre-intervention and end-intervention area under the curves. Area under the curve for glucagon during a mixed meal test.
Area under the curve for triglycerides during mixed meal test (mmol/L*min) -15 to 240 minutes from ingestion of standardized meal at time point 0 minutes. Comparison between pre-intervention and end-intervention area under the curves. Area under the curve for triglycerides during a mixed meal test.
Glycated hemoglobin (HbA1c) (mmol/mol) 12-week change. Comparison between pre-intervention and end-intervention glycated hemoglobin levels. Glycated hemoglobin (HbA1c) (mmol/mol)
Liver fat content (%) 12-week change. Comparison between pre-intervention scan and end-intervention scan. Measured with dixon-sequences scanning the abdomen and MR-Spectroscopy.
Visceral fat content (ml) 12-week change. Comparison between pre-intervention scan and end-intervention scan. Measured with dixon-sequences scanning the abdomen
Subcutaneous fat content (ml) 12-week change. Comparison between pre-intervention scan and end-intervention scan. Measured with dixon-sequences scanning the abdomen
One-week continuous glucose measurement Average glucose measured every 15 minutes for one week prior to study day 1 and 3. 12-week change. Comparison between pre-intervention measurement and end-intervention measurement. One-week continuous glucose measurement data.
Blood pressure (mmHg) 12-week change. Comparison between pre-intervention average ambulatory blood pressure and end-intervention average ambulatory blood pressure. Average daytime and night-time ambulatory blood pressure. 24-hour ambulatory blood pressure measurement, measured every 20 minutes during daytime and every 30 minutes during nighttime.
Food consumption in kilocalories (kcal) 12-week change. Comparison between pre-intervention food consumption and end-intervention food consumption. Food consumption is registered for 72-hours prior to study day 1 and 3. Food consumption is measured in kilocalories (kcal).
Trial Locations
- Locations (1)
Steno Diabetes Center Aarhus
🇩🇰Aarhus, Aarhus N, Denmark