fatty liver non-alcoholic fatty liver disease
Conditions
Interventions
During the first intervention period, participants will take once daily for 6
weeks a 300 mg tablet PF-06835919 or a an indistinguishable placebo. During the
second intervention period, the particip
Sponsors
Universiteit Maastricht
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: -Men and (postmenopausal) woman -Age: >= 40 and = 5.56%) -Stable dietary habits (no weight loss or gain >3 kg in the 3 months prior to inclusion) -Participants are able to provide signed and dated written informed consent prior to any study specific procedures
Exclusion criteria
Exclusion criteria: -Type 2 diabetes -Any contra-indication for MRI scanning -Patients with congestive heart failure and and/or severe renal and/or liver insufficiency -Uncontrolled hypertension -Alcohol consumption of >3 servings per day for man and >2 servings per day for woman -Smoking -Unstable body weight (weight loss or gain >3 kg in the 3 months prior to inclusion) -Engagement in structured exercise activities > 2 hours a week -Previous enrolment in a clinical study with an investigational product during the last 3 months or as judged by the Investigator which would possibly hamper our study results -Use of drugs that inhibit organic anion transporting polypeptide (OATP) transporters (e.g. rifampicin, gemfibrozil, cyclosporine, erythromcyin and clarithromycin) -Subjects who do not want to be informed about unexpected medical findings
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary outcome is hepatic insulin sensitivity, measured during the hyperinsulinemic euglycemic clamp as insulin-mediated suppression of endogenous glucose production, after 6 weeks of taking PF-06835919 compared to placebo. | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary outcomes are: -Intrahepatic lipid content measured during H-MRS -Liver lipid composition measured during H-MRS' -Amount of subcutaneous and visceral fat measured during MRI -Insulin-mediated suppression of free fatty acids measured in blood plasma taken during the hyperinsulinemic euglycemic clamp -Inflammatory markers measured in blood serum taken during the hyperinsulinemic euglycemic clamp -Resting energy expenditure measured by indirect calorimetry during the hyperinsulinemic euglycemic clamp -Sleep metabolic rate measure during the overnight stay in the respiration chamber -Body composition measured by the Bod Pod -Liver phosphomonoester levels as indication for ketohexokinase activity in the liver measured during P-MRS -Peripheral insulin sensitivity measured during the hyperinsulinemic euglycemic clamp -Metabolic flexibility measured during the hyperinsulinemic euglycemic clamp -Intramyocellular lipid content measured in the muscle biopsy -Short-chain fatty acids measured in fecal samples | — |
Countries
Netherlands
Outcome results
None listed