Clinical trial NCT05672433: 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
Overall status: UNKNOWN
Phase: NA
Conditions: Obesity, Abdominal
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Aarhus University Hospital
First posted: 2023-01-05
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Steady state plasma glucose during stage 2 of insulin suppression test (mmol/L)
timeFrame: 220, 230 and 240 minutes after test-start. Comparison between pre-intervention and end-intervention steady state plasma glucose.
measure: Steady state plasma glucose during stage 1 of insulin suppression test (mmol/L)
timeFrame: 100, 110 and 120 minutes after test-start. Comparison between pre-intervention and end-intervention steady state plasma glucose.
measure: Area under the curve for glucose during mixed meal test (mmol/L*min)
timeFrame: -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 outcomes:
measure: Area under the curve for insulin during mixed meal test (pmol/L*min)
timeFrame: -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.
measure: Area under the curve for glucagon during mixed meal test (pmol/L*min)
timeFrame: -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.
measure: Area under the curve for triglycerides during mixed meal test (mmol/L*min)
timeFrame: -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.
measure: Glycated hemoglobin (HbA1c) (mmol/mol)
timeFrame: 12-week change. Comparison between pre-intervention and end-intervention glycated hemoglobin levels.
measure: Liver fat content (%)
timeFrame: 12-week change. Comparison between pre-intervention scan and end-intervention scan.
measure: Visceral fat content (ml)
timeFrame: 12-week change. Comparison between pre-intervention scan and end-intervention scan.
measure: Subcutaneous fat content (ml)
timeFrame: 12-week change. Comparison between pre-intervention scan and end-intervention scan.
measure: One-week continuous glucose measurement
timeFrame: 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.
measure: Blood pressure (mmHg)
timeFrame: 12-week change. Comparison between pre-intervention average ambulatory blood pressure and end-intervention average ambulatory blood pressure.
measure: Food consumption in kilocalories (kcal)
timeFrame: 12-week change. Comparison between pre-intervention food consumption and end-intervention food consumption.
Other outcomes:
measure: Fasting glucose (mmol/l)
timeFrame: Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
measure: Fasting insulin (pmol/l)
timeFrame: Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
measure: Fasting total cholesterol (mmol/l),
timeFrame: Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
measure: Fasting HDL (mmol/l)
timeFrame: Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
measure: Fasting LDL (mmol/l)
timeFrame: Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
measure: Fasting triglycerides (mmol/l)
timeFrame: Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
measure: Fasting thyroid-stimulating hormone (international unit (IU)/l)
timeFrame: Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
measure: Fasting alanine aminotransferase (unit(U)/l)
timeFrame: Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
measure: Fasting high sensitivity c reactive protein (mg/l)
timeFrame: Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
measure: Fasting alpha-hydroxybutyrate (mmol/l)
timeFrame: Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
measure: Fasting C-terminal telopeptide (µg/l)
timeFrame: Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
measure: Fasting procollagen type 1 N-terminal propeptide (µg/l)
timeFrame: Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
measure: Fasting parathyroid hormone (pmol/l)
timeFrame: Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
measure: Fasting vitamin D (nmol/l)
timeFrame: Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
measure: Fasting ionized calcium (mmol/l)
timeFrame: Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
measure: Fasting monocyte chemoattractant protein-1 (pg/ml)
timeFrame: Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
measure: Fasting interleukin 1 (pg/ml)
timeFrame: Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
measure: Fasting interleukin 8 (pg/ml)
timeFrame: Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
measure: Fasting gastric inhibitory polypeptide (pmol/l)
timeFrame: Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
measure: Fasting glucagon-like peptide-2 (pmol/l)
timeFrame: Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
measure: Fasting growth/differentiation factor 15 (ng/l)
timeFrame: Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
measure: Fasting tumor necrosis factor (TNFα)
timeFrame: Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
measure: Fasting Homeostatic Model Assessment for Insulin Resistance by C-peptide (arbitrary unit).
timeFrame: Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
Locations:
city: Aarhus
country: Denmark
facility: Steno Diabetes Center Aarhus
state: Aarhus N
Study officials:
affiliation: Aarhus University Hospital
name: Søren Gregersen, M.D. Ph.D
role: PRINCIPAL_INVESTIGATOR
References: