Long-term Metabolic Effects of Cafestol

Not Applicable

• Conditions: Obesity, Abdominal

• 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.

Study Timeline

• Status Verified: 2022-06
• Study Start: 2022-06-28
• Study First Submitted: 2022-12-02
• Study First Submitted QC: 2023-01-04
• Last Update Submitted: 2023-01-04
• Study First Posted: 2023-01-05
• Last Update Posted: 2023-01-05
• Primary Completion: 2023-02-01
• Study Completion: 2023-03-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

Waist circumference > 102 cm (men) / 88 cm (women)

Exclusion Criteria

• 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

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