Living With Statins - The Impact of Cholesterol Lowering Drugs on Health, Lifestyle and Well-being

NCT02255682 | Completed Phase 4

• 1 other identifier: LIFESTAT - Observational Study
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

Background Statins are cholesterol lowering drugs that are prescribed to lower the risk of cardio-vascular diseases. The use of statins has increased markedly and it is now one of the most prescribed drugs in the world. 600,000 people in Denmark are taking statins on a daily basis, 40 % of these are taking the medication without having any other risk factors for cardio-vascular diseases than elevated blood-cholesterol i.e. they are in primary prevention. Statins are not without side effects and studies have shown that there is an elevated risk of developing diabetes when taking statins. This has led to an increased debate about the use of statins in primary prevention. Furthermore a large meta-analysis has shown that to prevent one event of cardio-vascular disease, it is necessary to treat 200 people for 3-5 years. These data suggest that more conservative use of statins to prevent CVD in otherwise healthy individuals at low risk for future CVD may be warranted. Other side effects of statins are muscle myalgia, muscle cramps and fatigue which potentially can prevent a physically active lifestyle. The biomedical background of these side effects is not fully elucidated but it has been shown that there is a link to decreasing levels of an important enzyme, Q10, which plays a role in muscle energy metabolism. Hypothesis The overarching research question is: why does statin treatment cause muscle pain? Does statin treatment impair (or even prevent) physical exercise training? Furthermore we would like to answer the following questions:

• Decreased muscle strength?
• Skeletal muscle inflammation?
• Decreased mitochondrial respiratory function?
• Abnormal glucose homeostasis?

Conditions

Cardiovascular Disease; Diabetes Mellitus

Keywords

physical activity; statin therapy; diabetes mellitus; cardiovascular disease; Q10-supplementation

Outcome Measures

Primary Outcomes (1)

• Difference in myalgia

  Difference in myalgia, measured by visual analog scale (VAS) between Simvastatin treated patients receiving Q10 or Q10-placebo.

  8 weeks

Secondary Outcomes (4)

• Difference in VO2-max

  8 weeks

• Difference in muscle strength

  8 weeks

• Difference in glucose metabolism

  8 weeks

• Difference in mitochondrial function

  8 weeks

Study Arms (2)

Simvastatin and Q10-placebo

PLACEBO COMPARATOR

Simvastatin 40 mg orally administered daily and Q10-placebo for 8 weeks

Drug: Simvastatin

Simvastatin and Q10

ACTIVE COMPARATOR

Simvastatin 40 mg orally administered daily for 8 weeks in combination with Q10 supplementation of 400 mg/daily

Drug: Simvastatin; Dietary Supplement: Q10

Interventions

Simvastatin DRUG

Also known as: Simvastatin Actavis, Simvastatin Hexal, Simvastatin KRKA, Simvastatin Orion, Simvastatin Sandoz, Simvastatin Stada, Simvastatin Teva, Zocor

Simvastatin and Q10; Simvastatin and Q10-placebo

Q10 DIETARY_SUPPLEMENT

Also known as: Bioquinon Q10

Simvastatin and Q10

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years.
• BMI 25-35.
• prescribed Simvastatin 40 mg/daily by their general practitioner.

You may not qualify if:

• Diabetes Mellitus.
• Cardiovascular disease such as arrythmia, ischaemic heart disease.
• Musculoskeletal disorders preventing the subject to perform physical.
• Mental disorders preventing the subject to understand the project description.

Sponsors & Collaborators

• University of Copenhagen: lead

Study Sites (1)

University of Copenhagen

Copenhagen, 2200, Denmark

Location

Related Publications (14)

• Boushel R, Gnaiger E, Schjerling P, Skovbro M, Kraunsoe R, Dela F. Patients with type 2 diabetes have normal mitochondrial function in skeletal muscle. Diabetologia. 2007 Apr;50(4):790-6. doi: 10.1007/s00125-007-0594-3. Epub 2007 Feb 15.

  PMID: 17334651 BACKGROUND

• Ebrahim S, Casas JP. Statins for all by the age of 50 years? Lancet. 2012 Aug 11;380(9841):545-7. doi: 10.1016/S0140-6736(12)60694-1. Epub 2012 May 17. No abstract available.

  PMID: 22607823 BACKGROUND

• Larsen S, Hey-Mogensen M, Rabol R, Stride N, Helge JW, Dela F. The influence of age and aerobic fitness: effects on mitochondrial respiration in skeletal muscle. Acta Physiol (Oxf). 2012 Jul;205(3):423-32. doi: 10.1111/j.1748-1716.2012.02408.x. Epub 2012 Feb 11.

  PMID: 22212519 BACKGROUND

• Larsen S, Nielsen J, Hansen CN, Nielsen LB, Wibrand F, Stride N, Schroder HD, Boushel R, Helge JW, Dela F, Hey-Mogensen M. Biomarkers of mitochondrial content in skeletal muscle of healthy young human subjects. J Physiol. 2012 Jul 15;590(14):3349-60. doi: 10.1113/jphysiol.2012.230185. Epub 2012 May 14.

  PMID: 22586215 BACKGROUND

• Larsen S, Stride N, Hey-Mogensen M, Hansen CN, Andersen JL, Madsbad S, Worm D, Helge JW, Dela F. Increased mitochondrial substrate sensitivity in skeletal muscle of patients with type 2 diabetes. Diabetologia. 2011 Jun;54(6):1427-36. doi: 10.1007/s00125-011-2098-4. Epub 2011 Mar 18.

  PMID: 21424396 BACKGROUND

• Larsen S, Stride N, Hey-Mogensen M, Hansen CN, Bang LE, Bundgaard H, Nielsen LB, Helge JW, Dela F. Simvastatin effects on skeletal muscle: relation to decreased mitochondrial function and glucose intolerance. J Am Coll Cardiol. 2013 Jan 8;61(1):44-53. doi: 10.1016/j.jacc.2012.09.036.

  PMID: 23287371 BACKGROUND

• Singh P, Kohr D, Kaps M, Blaes F. Skeletal muscle cell MHC I expression: implications for statin-induced myopathy. Muscle Nerve. 2010 Feb;41(2):179-84. doi: 10.1002/mus.21479.

  PMID: 19813190 BACKGROUND

• Cholesterol Treatment Trialists' (CTT) Collaborators; Mihaylova B, Emberson J, Blackwell L, Keech A, Simes J, Barnes EH, Voysey M, Gray A, Collins R, Baigent C. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet. 2012 Aug 11;380(9841):581-90. doi: 10.1016/S0140-6736(12)60367-5. Epub 2012 May 17.

  PMID: 22607822 BACKGROUND

• Parker BA, Thompson PD. Effect of statins on skeletal muscle: exercise, myopathy, and muscle outcomes. Exerc Sport Sci Rev. 2012 Oct;40(4):188-94. doi: 10.1097/JES.0b013e31826c169e.

  PMID: 23000957 BACKGROUND

• Perk J, De Backer G, Gohlke H, Graham I, Reiner Z, Verschuren WM, Albus C, Benlian P, Boysen G, Cifkova R, Deaton C, Ebrahim S, Fisher M, Germano G, Hobbs R, Hoes A, Karadeniz S, Mezzani A, Prescott E, Ryden L, Scherer M, Syvanne M, Scholte Op Reimer WJ, Vrints C, Wood D, Zamorano JL, Zannad F; Comitato per Linee Guida Pratiche (CPG) dell'ESC. [European Guidelines on Cardiovascular Disease Prevention in Clinical Practice (version 2012). The Fifth Joint Task Force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts)]. G Ital Cardiol (Rome). 2013 May;14(5):328-92. doi: 10.1714/1264.13964. No abstract available. Italian.

  PMID: 23612326 BACKGROUND

• Ray KK, Seshasai SR, Erqou S, Sever P, Jukema JW, Ford I, Sattar N. Statins and all-cause mortality in high-risk primary prevention: a meta-analysis of 11 randomized controlled trials involving 65,229 participants. Arch Intern Med. 2010 Jun 28;170(12):1024-31. doi: 10.1001/archinternmed.2010.182.

  PMID: 20585067 BACKGROUND

• Ridker PM, Pradhan A, MacFadyen JG, Libby P, Glynn RJ. Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial. Lancet. 2012 Aug 11;380(9841):565-71. doi: 10.1016/S0140-6736(12)61190-8.

  PMID: 22883507 BACKGROUND

• Taylor F, Ward K, Moore TH, Burke M, Davey Smith G, Casas JP, Ebrahim S. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2011 Jan 19;(1):CD004816. doi: 10.1002/14651858.CD004816.pub4.

  PMID: 21249663 BACKGROUND

• Dohlmann TL, Morville T, Kuhlman AB, Chrois KM, Helge JW, Dela F, Larsen S. Statin Treatment Decreases Mitochondrial Respiration But Muscle Coenzyme Q10 Levels Are Unaltered: The LIFESTAT Study. J Clin Endocrinol Metab. 2019 Jul 1;104(7):2501-2508. doi: 10.1210/jc.2018-01185.

  PMID: 30299473 DERIVED

MeSH Terms

Conditions

Cardiovascular Diseases; Diabetes Mellitus; Motor Activity

Interventions

Simvastatin; Tuberculin

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Behavior

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Antigens, Bacterial; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Antigens; Biological Factors

Study Officials

• Flemming Dela, MD, MDSci

  University of Copenhagen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: September 12, 2014
• First Posted: October 2, 2014
• Study Start: January 1, 2015
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: January 4, 2017

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)