Long-term Metabolic Effects of Cafestol

Does the Bioactive Substance in Coffee, Cafestol, Have Preventive Properties on Type-2-diabetes? (Long-term Substudy)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Obesity, Abdominal
• Intervention / Treatment: Dietary supplement: Cafestol; Dietary supplement: Placebo

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 Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Aarhus N
    • Aarhus, Aarhus N, Denmark, 8200
      • Steno Diabetes Center Aarhus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Cafestol; Participants in this arm ingest 6 mg cafestol capsules twice daily with breakfast and dinner.	Dietary supplement: Cafestol; Capsule with 6 mg cafestol twice daily
Placebo Comparator: Placebo; Participants in this arm ingest placebo capsules twice daily with breakfast and dinner.	Dietary supplement: Placebo; Capsule without cafestol twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Steady state plasma glucose during stage 2 of insulin suppression test (mmol/L)	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.	220, 230 and 240 minutes after test-start. Comparison between pre-intervention and end-intervention steady state plasma glucose.
Steady state plasma glucose during stage 1 of insulin suppression test (mmol/L)	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.	100, 110 and 120 minutes after test-start. Comparison between pre-intervention and end-intervention steady state plasma glucose.
Area under the curve for glucose during mixed meal test (mmol/L*min)	Area under the curve for glucose during a mixed meal test.	-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.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the curve for insulin during mixed meal test (pmol/L*min)	Area under the curve for insulin during a mixed meal test.	-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 mixed meal test (pmol/L*min)	Area under the curve for glucagon during a mixed meal test.	-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 mixed meal test (mmol/L*min)	Area under the curve for triglycerides during a mixed meal test.	-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.
Glycated hemoglobin (HbA1c) (mmol/mol)	Glycated hemoglobin (HbA1c) (mmol/mol)	12-week change. Comparison between pre-intervention and end-intervention glycated hemoglobin levels.
Liver fat content (%)	Measured with dixon-sequences scanning the abdomen and MR-Spectroscopy.	12-week change. Comparison between pre-intervention scan and end-intervention scan.
Visceral fat content (ml)	Measured with dixon-sequences scanning the abdomen	12-week change. Comparison between pre-intervention scan and end-intervention scan.
Subcutaneous fat content (ml)	Measured with dixon-sequences scanning the abdomen	12-week change. Comparison between pre-intervention scan and end-intervention scan.
One-week continuous glucose measurement	One-week continuous glucose measurement data.	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.
Blood pressure (mmHg)	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.	12-week change. Comparison between pre-intervention average ambulatory blood pressure and end-intervention average ambulatory blood pressure.
Food consumption in kilocalories (kcal)	Food consumption is registered for 72-hours prior to study day 1 and 3. Food consumption is measured in kilocalories (kcal).	12-week change. Comparison between pre-intervention food consumption and end-intervention food consumption.

Other Outcome Measures

Outcome Measure	Time Frame
Fasting glucose (mmol/l)	Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
Fasting insulin (pmol/l)	Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
Fasting total cholesterol (mmol/l),	Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
Fasting HDL (mmol/l)	Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
Fasting LDL (mmol/l)	Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
Fasting triglycerides (mmol/l)	Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
Fasting thyroid-stimulating hormone (international unit (IU)/l)	Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
Fasting alanine aminotransferase (unit(U)/l)	Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
Fasting high sensitivity c reactive protein (mg/l)	Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
Fasting alpha-hydroxybutyrate (mmol/l)	Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
Fasting C-terminal telopeptide (µg/l)	Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
Fasting procollagen type 1 N-terminal propeptide (µg/l)	Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
Fasting parathyroid hormone (pmol/l)	Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
Fasting vitamin D (nmol/l)	Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
Fasting ionized calcium (mmol/l)	Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
Fasting monocyte chemoattractant protein-1 (pg/ml)	Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
Fasting interleukin 1 (pg/ml)	Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
Fasting interleukin 8 (pg/ml)	Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
Fasting gastric inhibitory polypeptide (pmol/l)	Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
Fasting glucagon-like peptide-2 (pmol/l)	Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
Fasting growth/differentiation factor 15 (ng/l)	Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
Fasting tumor necrosis factor (TNFα)	Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
Fasting Homeostatic Model Assessment for Insulin Resistance by C-peptide (arbitrary unit).	Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Aarhus University Hospital
• Investigators: Principal Investigator: Søren Gregersen, M.D. Ph.D, Aarhus University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2022
• Primary Completion (Anticipated): February 1, 2023
• Study Completion (Anticipated): March 1, 2023

Study Registration Dates

• First Submitted: December 2, 2022
• First Submitted That Met QC Criteria: January 4, 2023
• First Posted (Actual): January 5, 2023

Study Record Updates

• Last Update Posted (Actual): January 5, 2023
• Last Update Submitted That Met QC Criteria: January 4, 2023
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Obesity; Obesity, Abdominal
• Other Study ID Numbers: cafestol.longterm

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No