Long-term Metabolic Effects of Cafestol

Obesity, Abdominal Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05672433
• Other study ID #: cafestol.longterm
• Status: Active, not recruiting
• Phase: N/A
• Start date: June 28, 2022
• Est. completion date: March 1, 2023

Study information

• Verified date: June 2022
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: March 1, 2023
• Est. primary completion date: February 1, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Obesity, Abdominal

Intervention

Dietary Supplement:
• Placebo
Capsule without cafestol twice daily
• Cafestol
Capsule with 6 mg cafestol twice daily

Locations

Country	Name	City	State
Denmark	Steno Diabetes Center Aarhus	Aarhus	Aarhus N

Sponsors (2)

Lead Sponsor	Collaborator
University of Aarhus	Aarhus University Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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.
Other	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.
Other	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.
Other	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.
Other	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.
Other	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.
Other	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.
Other	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.
Other	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.
Other	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.
Other	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.
Other	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.
Other	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.
Other	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.
Other	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.
Other	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.
Other	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.
Other	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.
Other	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.
Other	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.
Other	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.
Other	Fasting tumor necrosis factor (TNFa)		Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
Other	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.
Primary	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.
Primary	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.
Primary	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	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.
Secondary	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.
Secondary	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.
Secondary	Glycated hemoglobin (HbA1c) (mmol/mol)	Glycated hemoglobin (HbA1c) (mmol/mol)	12-week change. Comparison between pre-intervention and end-intervention glycated hemoglobin levels.
Secondary	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.
Secondary	Visceral fat content (ml)	Measured with dixon-sequences scanning the abdomen	12-week change. Comparison between pre-intervention scan and end-intervention scan.
Secondary	Subcutaneous fat content (ml)	Measured with dixon-sequences scanning the abdomen	12-week change. Comparison between pre-intervention scan and end-intervention scan.
Secondary	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.
Secondary	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.
Secondary	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.