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Long-term Metabolic Effects of Cafestol

Primary Purpose

Obesity, Abdominal

Status

Active

Phase

Not Applicable

Locations

Denmark

Study Type

Interventional

Intervention

Placebo

Cafestol

About this trial

This is an interventional prevention trial for Obesity, Abdominal

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Steno Diabetes Center Aarhus

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Cafestol

Placebo

Arm Description

Participants in this arm ingest 6 mg cafestol capsules twice daily with breakfast and dinner.

Participants in this arm ingest placebo capsules twice daily with breakfast and dinner.

Outcomes

Primary Outcome Measures

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.

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.

Area under the curve for glucose during mixed meal test (mmol/L*min)

Area under the curve for glucose during a mixed meal test.

Secondary Outcome Measures

Area under the curve for insulin during mixed meal test (pmol/L*min)

Area under the curve for insulin during a mixed meal test.

Area under the curve for glucagon during mixed meal test (pmol/L*min)

Area under the curve for glucagon during a mixed meal test.

Area under the curve for triglycerides during mixed meal test (mmol/L*min)

Area under the curve for triglycerides during a mixed meal test.

Glycated hemoglobin (HbA1c) (mmol/mol)

Liver fat content (%)

Measured with dixon-sequences scanning the abdomen and MR-Spectroscopy.

Visceral fat content (ml)

Measured with dixon-sequences scanning the abdomen

Subcutaneous fat content (ml)

Measured with dixon-sequences scanning the abdomen

One-week continuous glucose measurement

One-week continuous glucose measurement data.

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.

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).

Full Information

NCT ID

NCT05672433

First Posted

December 2, 2022

Last Updated

January 4, 2023

Sponsor

University of Aarhus

Collaborators

Aarhus University Hospital

1. Study Identification

Unique Protocol Identification Number

NCT05672433

Brief Title

Long-term Metabolic Effects of Cafestol

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2022

Overall Recruitment Status

Active, not recruiting

Study Start Date

June 28, 2022 (Actual)

Primary Completion Date

February 1, 2023 (Anticipated)

Study Completion Date

March 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Aarhus

Collaborators

Aarhus University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Obesity, Abdominal

7. Study Design

Primary Purpose

Prevention

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Cafestol

Arm Type

Active Comparator

Arm Description

Participants in this arm ingest 6 mg cafestol capsules twice daily with breakfast and dinner.

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Participants in this arm ingest placebo capsules twice daily with breakfast and dinner.

Intervention Type

Dietary Supplement

Intervention Name(s)

Placebo

Intervention Description

Capsule without cafestol twice daily

Intervention Type

Dietary Supplement

Intervention Name(s)

Cafestol

Intervention Description

Capsule with 6 mg cafestol twice daily

Primary Outcome Measure Information:

Title

Steady state plasma glucose during stage 2 of insulin suppression test (mmol/L)

Description

Time Frame

220, 230 and 240 minutes after test-start. Comparison between pre-intervention and end-intervention steady state plasma glucose.

Title

Steady state plasma glucose during stage 1 of insulin suppression test (mmol/L)

Description

Time Frame

100, 110 and 120 minutes after test-start. Comparison between pre-intervention and end-intervention steady state plasma glucose.

Title

Area under the curve for glucose during mixed meal test (mmol/L*min)

Description

Area under the curve for glucose during a mixed meal test.

Time Frame

-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 Measure Information:

Title

Area under the curve for insulin during mixed meal test (pmol/L*min)

Description

Area under the curve for insulin during a mixed meal test.

Time Frame

-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.

Title

Area under the curve for glucagon during mixed meal test (pmol/L*min)

Description

Area under the curve for glucagon during a mixed meal test.

Time Frame

-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.

Title

Area under the curve for triglycerides during mixed meal test (mmol/L*min)

Description

Area under the curve for triglycerides during a mixed meal test.

Time Frame

-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.

Title

Glycated hemoglobin (HbA1c) (mmol/mol)

Description

Glycated hemoglobin (HbA1c) (mmol/mol)

Time Frame

12-week change. Comparison between pre-intervention and end-intervention glycated hemoglobin levels.

Title

Liver fat content (%)

Description

Measured with dixon-sequences scanning the abdomen and MR-Spectroscopy.

Time Frame

12-week change. Comparison between pre-intervention scan and end-intervention scan.

Title

Visceral fat content (ml)

Description

Measured with dixon-sequences scanning the abdomen

Time Frame

12-week change. Comparison between pre-intervention scan and end-intervention scan.

Title

Subcutaneous fat content (ml)

Description

Measured with dixon-sequences scanning the abdomen

Time Frame

12-week change. Comparison between pre-intervention scan and end-intervention scan.

Title

One-week continuous glucose measurement

Description

One-week continuous glucose measurement data.

Time Frame

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.

Title

Blood pressure (mmHg)

Description

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.

Time Frame

12-week change. Comparison between pre-intervention average ambulatory blood pressure and end-intervention average ambulatory blood pressure.

Title

Food consumption in kilocalories (kcal)

Description

Food consumption is registered for 72-hours prior to study day 1 and 3. Food consumption is measured in kilocalories (kcal).

Time Frame

12-week change. Comparison between pre-intervention food consumption and end-intervention food consumption.

Other Pre-specified Outcome Measures:

Title

Fasting glucose (mmol/l)

Time Frame