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Effect of Fluvastatin on Brown Fat Activity (FluvaBAT)

Primary Purpose

Adipose Tissue, Brown, Insulin Resistance, Clinical Trial

Status
Completed
Phase
Phase 4
Locations
Switzerland
Study Type
Interventional
Intervention
Fluvastatin
Sponsored by
University of Zurich
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Adipose Tissue, Brown focused on measuring Brown Adipose Tissue, Brown Fat, Fluvastatin, Prospective Clinical Trial

Eligibility Criteria

18 Years - 40 Years (Adult)MaleAccepts Healthy Volunteers

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)

Sites / Locations

  • University Hospital of Zurich, PET/MR Center
  • University Hospital of Basel

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Experimental

Arm Description

Volunteers receive calorimetric tests and FDG PET scans pre and post 2 weeks of Fluvastatine.

Outcomes

Primary Outcome Measures

(18)F-FDG uptake in the supraclavicular brown adipose tissue measured by PET by the maximum standardized uptake value (SUVmax)
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

The mean standardized uptake value for 18F-FDG uptake (SUVmean) in the supraclavicular adipose tissue depot
SUVmean in the supraclavicular adipose tissue depot (analog. SUVmax)
Volume of supraclavicular BAT
Volume of supraclavicular BAT as determined on Magnetic Resonance Imaging (MRI)
fat fraction with T2 relaxation time of the BAT depot
fat fraction with T2 relaxation time of the scBAT depot as determined by MRI
Cold induced thermogenesis
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
Supraclavicular skin temperature in response to mild cold stimulus measured by local probe

Full Information

First Posted
June 12, 2017
Last Updated
May 28, 2018
Sponsor
University of Zurich
Collaborators
University of Basel
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1. Study Identification

Unique Protocol Identification Number
NCT03189511
Brief Title
Effect of Fluvastatin on Brown Fat Activity
Acronym
FluvaBAT
Official Title
Short Term Effect of Fluvastatin on Brown Adipose Tissue Thermogenesis and Activity in Humans
Study Type
Interventional

2. Study Status

Record Verification Date
May 2018
Overall Recruitment Status
Completed
Study Start Date
May 31, 2017 (Actual)
Primary Completion Date
January 23, 2018 (Actual)
Study Completion Date
February 19, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Zurich
Collaborators
University of Basel

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adipose Tissue, Brown, Insulin Resistance, Clinical Trial
Keywords
Brown Adipose Tissue, Brown Fat, Fluvastatin, Prospective Clinical Trial

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Sequential Assignment
Model Description
Open-label non-randomized historic control (before-after) trial
Masking
None (Open Label)
Enrollment
17 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Experimental
Arm Type
Experimental
Arm Description
Volunteers receive calorimetric tests and FDG PET scans pre and post 2 weeks of Fluvastatine.
Intervention Type
Drug
Intervention Name(s)
Fluvastatin
Other Intervention Name(s)
Lescol
Intervention Description
Fluvastatin 40 mg twice daily per mouth for 14 days.
Primary Outcome Measure Information:
Title
(18)F-FDG uptake in the supraclavicular brown adipose tissue measured by PET by the maximum standardized uptake value (SUVmax)
Description
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.
Time Frame
14 days
Secondary Outcome Measure Information:
Title
The mean standardized uptake value for 18F-FDG uptake (SUVmean) in the supraclavicular adipose tissue depot
Description
SUVmean in the supraclavicular adipose tissue depot (analog. SUVmax)
Time Frame
14 days
Title
Volume of supraclavicular BAT
Description
Volume of supraclavicular BAT as determined on Magnetic Resonance Imaging (MRI)
Time Frame
14 days
Title
fat fraction with T2 relaxation time of the BAT depot
Description
fat fraction with T2 relaxation time of the scBAT depot as determined by MRI
Time Frame
14 days
Title
Cold induced thermogenesis
Description
Cold induced thermogenesis: Increase in energy expenditure above resting metabolic rate in response to a mild cold stimulus and pharmacologic stimulation with Mirabegron.
Time Frame
14 days
Title
Supraclavicular skin temperature in response to mild cold stimulus
Description
Supraclavicular skin temperature in response to mild cold stimulus measured by local probe
Time Frame
14 days

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Irene A Burger, M.D.
Organizational Affiliation
University of Zurich
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital of Zurich, PET/MR Center
City
Schlieren
State/Province
Zurich
ZIP/Postal Code
8952
Country
Switzerland
Facility Name
University Hospital of Basel
City
Basel
ZIP/Postal Code
4031
Country
Switzerland

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
25565203
Citation
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Results Reference
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21693744
Citation
Preiss D, Seshasai SR, Welsh P, Murphy SA, Ho JE, Waters DD, DeMicco DA, Barter P, Cannon CP, Sabatine MS, Braunwald E, Kastelein JJ, de Lemos JA, Blazing MA, Pedersen TR, Tikkanen MJ, Sattar N, Ray KK. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA. 2011 Jun 22;305(24):2556-64. doi: 10.1001/jama.2011.860.
Results Reference
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PubMed Identifier
24152688
Citation
Puurunen J, Piltonen T, Puukka K, Ruokonen A, Savolainen MJ, Bloigu R, Morin-Papunen L, Tapanainen JS. Statin therapy worsens insulin sensitivity in women with polycystic ovary syndrome (PCOS): a prospective, randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab. 2013 Dec;98(12):4798-807. doi: 10.1210/jc.2013-2674. Epub 2013 Oct 23.
Results Reference
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PubMed Identifier
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Citation
Duvnjak L, Blaslov K. Statin treatment is associated with insulin sensitivity decrease in type 1 diabetes mellitus: A prospective, observational 56-month follow-up study. J Clin Lipidol. 2016 Jul-Aug;10(4):1004-1010. doi: 10.1016/j.jacl.2016.04.012. Epub 2016 May 10.
Results Reference
background
PubMed Identifier
23471546
Citation
Chapple CR, Dvorak V, Radziszewski P, Van Kerrebroeck P, Wyndaele JJ, Bosman B, Boerrigter P, Drogendijk T, Ridder A, Van Der Putten-Slob I, Yamaguchi O; Dragon Investigator Group. A phase II dose-ranging study of mirabegron in patients with overactive bladder. Int Urogynecol J. 2013 Sep;24(9):1447-58. doi: 10.1007/s00192-013-2042-x. Epub 2013 Mar 8.
Results Reference
background
PubMed Identifier
33225717
Citation
Loeliger RC, Maushart CI, Gashi G, Senn JR, Felder M, Becker AS, Muller J, Balaz M, Wolfrum C, Burger IA, Betz MJ. Relation of diet-induced thermogenesis to brown adipose tissue activity in healthy men. Am J Physiol Endocrinol Metab. 2021 Jan 1;320(1):E93-E101. doi: 10.1152/ajpendo.00237.2020. Epub 2020 Nov 23.
Results Reference
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PubMed Identifier
32699996
Citation
Fischer JGW, Maushart CI, Becker AS, Muller J, Madoerin P, Chirindel A, Wild D, Ter Voert EEGW, Bieri O, Burger I, Betz MJ. Comparison of [18F]FDG PET/CT with magnetic resonance imaging for the assessment of human brown adipose tissue activity. EJNMMI Res. 2020 Jul 22;10(1):85. doi: 10.1186/s13550-020-00665-7.
Results Reference
derived

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Effect of Fluvastatin on Brown Fat Activity

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