Effect of Fluvastatin on Brown Fat Activity

Phase 4

Completed

• Conditions: Adipose Tissue, Brown; Insulin Resistance; Clinical Trial
• Interventions: Drug: Fluvastatin

• Registration Number: NCT03189511
• Lead Sponsor: University of Zurich

Brief Summary

The purpose of this study is to elucidate the effects of Fluvastatin on brown adipose tissue activity in humans.

Detailed Description

Statins, inhibitors of cholesterol biosynthesis, act by inhibiting the enzyme of the mevalonate pathway. Although the clinical benefits of statins are undisputable, they have been shown to increase insulin resistance and incidence of type 2 diabetes mellitus, the mechanism of which is currently not clear.

The main function of brown adipose tissue (BAT) is non-shivering thermogenesis (i.e. heat production through energy dissipation) in brown adipocytes. There has been a growing interest in BAT as a novel therapeutic approach to increase energy expenditure in order to facilitate weight-loss and increase insulin sensitivity.

BAT activity will be assessed using calorimetric test and \[18F\]-Fluorodeoxyglucose (FDG) positron emission tomography (PET).

We speculate that statins inhibit BAT function and that this mechanism may contribute to the above mentioned increase in insulin resistance.

Study Timeline

• Study Start: 2017-05-31
• Study First Submitted: 2017-06-12
• Study First Submitted QC: 2017-06-13
• Study First Posted: 2017-06-16
• Primary Completion: 2018-01-23
• Study Completion: 2018-02-19
• Status Verified: 2018-05
• Last Update Submitted: 2018-05-28
• Last Update Posted: 2018-05-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 17

Inclusion Criteria

• Male volunteers (18-40 y)
• body mass index 19 to 27 kg/m²
• Fluent in German or English

Exclusion Criteria

• Regular physical exercise of more than >150 min of exercise per week.
• Contraindications to the class of drugs under study, e.g. known hypersensitivity or allergy to class of drugs or the investigational product,
• Other clinically significant concomitant disease states (e.g., renal failure, hepatic dysfunction, cardiovascular disease, etc.),
• Clinically indicated intake of the following medications: Corticosteroids, CYP3A4-Inhibitors (Itraconazol, Voriconazol, Fluconazol, Clarithromycin, Erythromycin, Indinavir, Nelfinavir, Ritonavir, Grapefruit juice), Beta-Blocker, Neuroleptics, Tricyclic Antidepressants,
• Known or suspected non-compliance, drug or alcohol abuse,
• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant,
• Participation in another study with investigational drug within the 30 days preceding and during the present study,
• Participation in another study involving ionizing radiation in the same year,
• Previous enrolment into the current study,
• Enrolment of the investigator, his/her family members, employees and other dependent persons,
• MRI contraindications: Not MRI-compatible metal in the body, cardiac pacemaker, History of surgery with possible metal clips/parts still in the body, claustrophobia.
• Resting pulse rate > 70 bpm
• Known arterial hypertension or resting blood pressure > 130/80 mmHg.
• frequence corrected QT-time (QTc) >430 ms
• Serum creatinine > 1.5x upper limit of norm (ULN), i.e.> 145 µmol/L
• creatine kinase > 1.5x ULN, i.e. > 300 U/L
• aspartate transaminase (ASAT) > 1.5x ULN, i.e. > 51 U/L
• alanine aminotransferase (ALAT) > 1.5x ULN, i.e. > 88 U/L
• Hypothyroidism
• Vitamin D deficiency, Vitamin D3 < 25 nmol/L
• Intake of anticoagulants or inhibitors of platelet aggregation (e.g. Aspirin, clopidogrel).
• Known tendency to form keloids (hypertrophic scar tissue)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Experimental	Fluvastatin	Volunteers receive calorimetric tests and FDG PET scans pre and post 2 weeks of Fluvastatine.

Primary Outcome Measures

Name	Time	Method
(18)F-FDG uptake in the supraclavicular brown adipose tissue measured by PET by the maximum standardized uptake value (SUVmax)	14 days	Cold and Mirabegron induced 18F-FDG uptake into the supra-clavicular brown adipose tissue (scBAT) as determined by 18F-FDG PET/MR standardized uptake value (SUVmax) after two weeks of treatment with Fluvastatin.

Secondary Outcome Measures

Name	Time	Method
The mean standardized uptake value for 18F-FDG uptake (SUVmean) in the supraclavicular adipose tissue depot	14 days	SUVmean in the supraclavicular adipose tissue depot (analog. SUVmax)
Volume of supraclavicular BAT	14 days	Volume of supraclavicular BAT as determined on Magnetic Resonance Imaging (MRI)
fat fraction with T2 relaxation time of the BAT depot	14 days	fat fraction with T2 relaxation time of the scBAT depot as determined by MRI
Cold induced thermogenesis	14 days	Cold induced thermogenesis: Increase in energy expenditure above resting metabolic rate in response to a mild cold stimulus and pharmacologic stimulation with Mirabegron.
Supraclavicular skin temperature in response to mild cold stimulus	14 days	Supraclavicular skin temperature in response to mild cold stimulus measured by local probe

Trial Locations

Locations (2)

University Hospital of Basel; 🇨🇭 Basel, Switzerland

University Hospital of Zurich, PET/MR Center; 🇨🇭 Schlieren, Zurich, Switzerland