Cardiovascular DiseasePhase 4LIFESTATNCT02796378
Living With Statins - Interventional Exercise Study
A Phase 4 study testing Training+Simvastatin+Q10 in people with Cardiovascular Disease and Diabetes Mellitus, run by University of Copenhagen at 1 site in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 to 70 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Cardiovascular Disease, Diabetes Mellitus
- What is being tested?
- Training+Simvastatin+Q10
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteDenmark
- Study dates
- Jun 2016to Dec 2021
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 70 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Elevated blood-cholesterol
Who cannot join
- Cholesterol-lowering drugs
- Diabetes Mellitus
- Cardiovascular disease such as arrythmia, ischaemic heart disease.
- Musculoskeletal disorders preventing the subject to perform physical training
- Mental disorders preventing the subject to understand the project description.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Living With Statins - The Impact of Cholesterol Lowering Drugs on Health, Lifestyle and Well-being
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. More than 600,000 people in Denmark are taking statins on a daily basis, approximately 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.
Read more
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 prohibit) physical exercise training? Furthermore the following questions will be investigated:
- Does statin treatment cause:
- Decreased muscle strength?
- Skeletal muscle inflammation?
- Decreased mitochondrial respiratory function? B. Abnormal glucose homeostasis?
Re question A \& B: If so, can physical training counteract this effect of statin treatment?
Read the detailed description
Background:
Hypercholesterolemia and statin use in Denmark
Simvastatin is the most commonly prescribed statin, a class of drugs that inhibit hydroxyl-methyl-glutaryl (HMG) coenzyme A reductase, and thereby blocking biosynthesis of cholesterol in the liver. Simvastatin is prescribed for individuals with elevated low-density lipoprotein cholesterol (LDL-C) and/or total cholesterol, because these clinical parameters are viewed as a risk factor for cardiovascular-disease (CVD), even in the absence of other health problems or risk factors, such as previous myocardial infarction, diabetes or hypertension.
Approximately 40% of the prescriptions for statins are issued for primary prevention of elevated cholesterol by general practitioners to patients without bodily symptoms or signs. Only the "cholesterol number" makes the risk of heart attack and stroke visible. The lack of symptoms is likely to be of importance for patients' adherence to treatment as is adverse effects. A number of factors, such as information in mass media and changes in daily life, may affect the decision to take the treatment
Treatment guidelines for hypercholesterolemia:
The guidelines indicate preventive treatment with statins is appropriate in individuals with >10% predicted risk of a major vascular event within 5 years, while, some, but not all opinion-leaders advocate a 5% threshold. Nevertheless, statin therapy failed to reduce all-cause mortality in a meta-study of 65,229 patients without CVD, some of whom had diabetes. Similarly, a Cochrane review analysis, which included some studies in which more than 10% of the patients had history of CVD, showed only 0.5% reduction in all-cause mortality, indicating that for every 200 patients taking statins daily for 5 years, 1 death would be prevented. 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.
The downside:
Rhabdomyolysis (skeletal muscle cell death) is an infrequent but serious side-effect of statin use, that can on rare occasion lead to acute renal failure and death (i.e., 1.5 deaths per 106 prescriptions). Statin use is much more frequently associated with muscle dysfunction, including myalgia (muscle pain), cramps, and weakness. The reported incidence of myalgia varies from 1% (pharmaceutical company reports) to as high as 75% in statin-treated athletes. Mild to severe myalgia is a strong disincentive to regular exercise, and because regular exercise is one of the critical life-style approaches to preventing CVD and reducing blood cholesterol, this is a significant down-side of statin use. Regular exercise is also effective in preventing and treating obesity and type 2 diabetes, which themselves are risk factors for CVD.
The mechanism behind the myalgia is not known. However, the investigators behind this study has recently demonstrated that muscle mitochondrial function is impaired with statin treatment and the Q10 protein may play a key role in this. In addition, the statins also negatively affect the glucose tolerance, increasing the risk of type 2 diabetes.
Research questions:
The overarching research question is: why does statin treatment cause muscle pain? Does statin treatment impair (or even prohibit) physical exercise training? Furthermore the following questions will be investigated:
- Does statin treatment cause:
- Decreased muscle strength?
- Skeletal muscle inflammation?
- Decreased mitochondrial respiratory function? B. Abnormal glucose homeostasis?
Re question A \& B: If so, can physical training counteract this effect of statin treatment?
Methodology:
Cohort
Patients that fulfil defined inclusion and exclusion criteria will be recruited from General Practice clinics in Copenhagen and news paper advertisements. The vast majority of these patients are being assessed on basis of the HeartScore risk estimation system that offers direct estimation of the ten-year risk of fatal cardiovascular disease in a format suited to the constraints of clinical practice. A staggered recruitment will be implemented.
30 men (age: 40-70 years; BMI: 25-35 kg/m2) before initiation of a statin treatment as primary prevention are recruited. No other risk factors for CVD except elevated total cholesterol (>6 mmol/l) and/or elevated LDL cholesterol (>3,5 mmol/l) and mild hypertension (<160/100 mm Hg) must be present.
The patients will be allocated (randomization by drawing a lot) to one of three groups:
- Physical exercise training and Simvastatin 40 mg/day and Q10 placebo
- Physical exercise training and Simvastatin 40 mg/day and Q10 400 mg/day supplementation
- Physical exercise training, Simvastatin placebo and Q10 placebo
The intervention period is 8 weeks with a series of experimental days before and after.
Experimental days (identical before and after the interventions):
Information day: health examination, ECG and Maximal oxygen uptake take (VO2 max).
Day 1 (overnight fasting, approximately 5 hours):
- Dual energy x-ray absorptiometry (DXA) scan (body composition and body fat).
- Oral glucose tolerance test + score questionnaire for muscle pain/discomfort (incl. Visual Analog Scale)
- Isokinetic strength and Rate of Force Development (PowerRig and KinCom dynamometer).
- Repeated VO2-max-test
Day 2 (overnight fasting approximately 7 hours):
- Muscle biopsy, vastus lateralis
- 2 step Euglycemic, hyperinsulinaemic clamp.
Training programme All training is supervised and takes place at the department. The training is aerobic, bicycle ergometer training (45 min/session at 60-70% of VO2max) three times a week for 8 weeks.
- Conditions
- Cardiovascular Disease, Diabetes Mellitus
- Being tested
- Training+Simvastatin+Q10-placebo, Training+Simvastatin-placebo+Q10-placebo, Training+Simvastatin+Q10
- Keywords
- physical activity, statin therapy, diabetes mellitus, cardiovascular disease, Q10-supplementation
- Medical subject headings
- Cardiovascular Diseases, Diabetes Mellitus, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Training+Simvastatin+Q10-placeboDrug
Also called SP
8 weeks of exercise training on a bycycle ergometer 3 times/week combined with Simvastatin 40 mg/day and Q10-placebo.
Training+Simvastatin-placebo+Q10-placeboDrug
Also called PL
8 weeks of exercise training on a bycycle ergometer 3 times/week combined with Simvastatin-placebo and Q10-placebo.
Training+Simvastatin+Q10Drug
Also called Simvastatin KRKA, SQ
8 weeks of exercise training on a bycycle ergometer 3 times/week combined with Simvastatin 40 mg/day and Q10 400 mg/day.
| Study group | Role | What they receive |
|---|---|---|
| Training+Simvastatin+Q10-placebo | Active comparator | Training+Simvastatin+Q10-placebo. 8 Weeks of exercise training on a bicycle ergometer three times a week and 40 mg of Simvastatin pr day and Q10-placebo. Receives: Drug: Training+Simvastatin+Q10-placebo |
| Training+Simvastatin-placebo+Q10-placebo | Placebo comparator | Training+Simvastatin-placebo+Q10-placebo. 8 Weeks of exercise training on a bicycle ergometer three times a week, Simvastatin-placebo and Q10-placebo. Receives: Drug: Training+Simvastatin-placebo+Q10-placebo |
| Training+Simvastatin+Q10 | Active comparator | Training+Simvastatin+Q10. 8 Weeks of exercise training on a bicycle ergometer three times a week and 40 mg of Simvastatin pr day in combination with 400 mg of oral supplementation with Q10. Receives: Drug: Training+Simvastatin+Q10 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Physical performance measured by VO2-max
Difference in physical performance measured by VO2-max (mlO2/min/kgBW) in the three different intervention groups.
Measured: 8 weeks
Secondary outcomes (4)
Myalgia measured by VAS
Difference in potential myalgia, measured by visual analog scale (VAS) between the three different intervention groups.
Measured: 8 weeks
Difference in muscle strength measured by KinCom dynamometer and PowerRig
Difference in muscle strength between the three different intervention groups.
Measured: 8 weeks
Difference in glucose metabolism measured by hyperinsulinemic euglycemic clamp
Difference in glucose metabolism between the three different intervention groups.
Measured: 8 weeks
Difference in mitochondrial function measured by respirometry
Difference in mitochondrial function between the three different intervention groups.
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2016 (estimated)
- Study startJun 2016
- Primary completionJul 2021 (estimated)
- Study completionDec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Cardiovascular DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Copenhagen
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Flemming Dela, University of Copenhagen
- Investigators
- Flemming Dela, MD, MDSci, Principal investigator, University of Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02796378
- Sponsor's protocol ID
- LIFESTAT - Exercise study
- Acronym
- LIFESTAT
- Status last verified
- Feb 2021
- First submitted
- 27 May 2016
- Last updated
- 11 Feb 2021
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 17334651Ebrahim 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.
PubMed 22607823Larsen 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.
PubMed 22212519Larsen 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.
PubMed 22586215Larsen 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.
PubMed 21424396Larsen 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.
PubMed 23287371Singh 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.
PubMed 19813190Cholesterol 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.
PubMed 22607822Parker 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.
PubMed 23000957Perk 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.
PubMed 23612326Ray 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.
PubMed 20585067Ridker 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.
PubMed 22883507Taylor 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.
PubMed 21249663
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Living With Statins - The Impact of Cholesterol Lowering Drugs on Health, Lifestyle and Well-being
- ClinicalTrials.gov ID
- NCT02796378
- Acronym / sponsor ID
- LIFESTAT / LIFESTAT - Exercise study
- Conditions
- Cardiovascular Disease, Diabetes Mellitus
- Keywords
- physical activity, statin therapy, diabetes mellitus, cardiovascular disease, Q10-supplementation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- University of CopenhagenUniversity, hospital or other
- Study start
- Jun 2016
- Primary completion
- Jul 2021 (estimated)
- Study completion
- Dec 2021 (estimated)
- First posted
- 10 Jun 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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. More than 600,000 people in Denmark are taking statins on a daily basis, approximately 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 prohibit) physical exercise training? Furthermore the following questions will be investigated:
- Does statin treatment cause:
- Decreased muscle strength?
- Skeletal muscle inflammation?
- Decreased mitochondrial respiratory function? B. Abnormal glucose homeostasis?
Re question A \& B: If so, can physical training counteract this effect of statin treatment?
Detailed description
Background:
Hypercholesterolemia and statin use in Denmark
Simvastatin is the most commonly prescribed statin, a class of drugs that inhibit hydroxyl-methyl-glutaryl (HMG) coenzyme A reductase, and thereby blocking biosynthesis of cholesterol in the liver. Simvastatin is prescribed for individuals with elevated low-density lipoprotein cholesterol (LDL-C) and/or total cholesterol, because these clinical parameters are viewed as a risk factor for cardiovascular-disease (CVD), even in the absence of other health problems or risk factors, such as previous myocardial infarction, diabetes or hypertension.
Approximately 40% of the prescriptions for statins are issued for primary prevention of elevated cholesterol by general practitioners to patients without bodily symptoms or signs. Only the "cholesterol number" makes the risk of heart attack and stroke visible. The lack of symptoms is likely to be of importance for patients' adherence to treatment as is adverse effects. A number of factors, such as information in mass media and changes in daily life, may affect the decision to take the treatment
Treatment guidelines for hypercholesterolemia:
The guidelines indicate preventive treatment with statins is appropriate in individuals with >10% predicted risk of a major vascular event within 5 years, while, some, but not all opinion-leaders advocate a 5% threshold. Nevertheless, statin therapy failed to reduce all-cause mortality in a meta-study of 65,229 patients without CVD, some of whom had diabetes. Similarly, a Cochrane review analysis, which included some studies in which more than 10% of the patients had history of CVD, showed only 0.5% reduction in all-cause mortality, indicating that for every 200 patients taking statins daily for 5 years, 1 death would be prevented. 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.
The downside:
Rhabdomyolysis (skeletal muscle cell death) is an infrequent but serious side-effect of statin use, that can on rare occasion lead to acute renal failure and death (i.e., 1.5 deaths per 106 prescriptions). Statin use is much more frequently associated with muscle dysfunction, including myalgia (muscle pain), cramps, and weakness. The reported incidence of myalgia varies from 1% (pharmaceutical company reports) to as high as 75% in statin-treated athletes. Mild to severe myalgia is a strong disincentive to regular exercise, and because regular exercise is one of the critical life-style approaches to preventing CVD and reducing blood cholesterol, this is a significant down-side of statin use. Regular exercise is also effective in preventing and treating obesity and type 2 diabetes, which themselves are risk factors for CVD.
The mechanism behind the myalgia is not known. However, the investigators behind this study has recently demonstrated that muscle mitochondrial function is impaired with statin treatment and the Q10 protein may play a key role in this. In addition, the statins also negatively affect the glucose tolerance, increasing the risk of type 2 diabetes.
Research questions:
The overarching research question is: why does statin treatment cause muscle pain? Does statin treatment impair (or even prohibit) physical exercise training? Furthermore the following questions will be investigated:
- Does statin treatment cause:
- Decreased muscle strength?
- Skeletal muscle inflammation?
- Decreased mitochondrial respiratory function? B. Abnormal glucose homeostasis?
Re question A \& B: If so, can physical training counteract this effect of statin treatment?
Methodology:
Cohort
Patients that fulfil defined inclusion and exclusion criteria will be recruited from General Practice clinics in Copenhagen and news paper advertisements. The vast majority of these patients are being assessed on basis of the HeartScore risk estimation system that offers direct estimation of the ten-year risk of fatal cardiovascular disease in a format suited to the constraints of clinical practice. A staggered recruitment will be implemented.
30 men (age: 40-70 years; BMI: 25-35 kg/m2) before initiation of a statin treatment as primary prevention are recruited. No other risk factors for CVD except elevated total cholesterol (>6 mmol/l) and/or elevated LDL cholesterol (>3,5 mmol/l) and mild hypertension (<160/100 mm Hg) must be present.
The patients will be allocated (randomization by drawing a lot) to one of three groups:
- Physical exercise training and Simvastatin 40 mg/day and Q10 placebo
- Physical exercise training and Simvastatin 40 mg/day and Q10 400 mg/day supplementation
- Physical exercise training, Simvastatin placebo and Q10 placebo
The intervention period is 8 weeks with a series of experimental days before and after.
Experimental days (identical before and after the interventions):
Information day: health examination, ECG and Maximal oxygen uptake take (VO2 max).
Day 1 (overnight fasting, approximately 5 hours):
- Dual energy x-ray absorptiometry (DXA) scan (body composition and body fat).
- Oral glucose tolerance test + score questionnaire for muscle pain/discomfort (incl. Visual Analog Scale)
- Isokinetic strength and Rate of Force Development (PowerRig and KinCom dynamometer).
- Repeated VO2-max-test
Day 2 (overnight fasting approximately 7 hours):
- Muscle biopsy, vastus lateralis
- 2 step Euglycemic, hyperinsulinaemic clamp.
Training programme All training is supervised and takes place at the department. The training is aerobic, bicycle ergometer training (45 min/session at 60-70% of VO2max) three times a week for 8 weeks.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Training+Simvastatin+Q10-placebo | Active comparator | Drug: Training+Simvastatin+Q10-placeboTraining+Simvastatin+Q10-placebo. 8 Weeks of exercise training on a bicycle ergometer three times a week and 40 mg of Simvastatin pr day and Q10-placebo. |
| Training+Simvastatin-placebo+Q10-placebo | Placebo comparator | Drug: Training+Simvastatin-placebo+Q10-placeboTraining+Simvastatin-placebo+Q10-placebo. 8 Weeks of exercise training on a bicycle ergometer three times a week, Simvastatin-placebo and Q10-placebo. |
| Training+Simvastatin+Q10 | Active comparator | Drug: Training+Simvastatin+Q10Training+Simvastatin+Q10. 8 Weeks of exercise training on a bicycle ergometer three times a week and 40 mg of Simvastatin pr day in combination with 400 mg of oral supplementation with Q10. |
Who may qualify
- Ages
- 40 to 70 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Elevated blood-cholesterol
Key exclusion criteria (5 listed)
- Cholesterol-lowering drugs
- Diabetes Mellitus
- Cardiovascular disease such as arrythmia, ischaemic heart disease.
- Musculoskeletal disorders preventing the subject to perform physical training
- Mental disorders preventing the subject to understand the project description.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Training+Simvastatin+Q10-placeboAlso: SP8 weeks of exercise training on a bycycle ergometer 3 times/week combined with Simvastatin 40 mg/day and Q10-placebo. | Drug | Training+Simvastatin+Q10-placebo |
| Training+Simvastatin-placebo+Q10-placeboAlso: PL8 weeks of exercise training on a bycycle ergometer 3 times/week combined with Simvastatin-placebo and Q10-placebo. | Drug | Training+Simvastatin-placebo+Q10-placebo |
| Training+Simvastatin+Q10Also: Simvastatin KRKA, SQ8 weeks of exercise training on a bycycle ergometer 3 times/week combined with Simvastatin 40 mg/day and Q10 400 mg/day. | Drug | Training+Simvastatin+Q10 |
Primary outcome
Physical performance measured by VO2-max
Time frame: 8 weeks
Difference in physical performance measured by VO2-max (mlO2/min/kgBW) in the three different intervention groups.
4 secondary outcomes
Myalgia measured by VAS
Time frame: 8 weeks
Difference in muscle strength measured by KinCom dynamometer and PowerRig
Time frame: 8 weeks
Difference in glucose metabolism measured by hyperinsulinemic euglycemic clamp
Time frame: 8 weeks
Difference in mitochondrial function measured by respirometry
Time frame: 8 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2021.
- Background: PubMed 17334651Boushel 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.
- Background: PubMed 22607823Ebrahim 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.
- Background: PubMed 22212519Larsen 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.
- Background: PubMed 22586215Larsen 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.
- Background: PubMed 21424396Larsen 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.
- Background: PubMed 23287371Larsen 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.
- Background: PubMed 19813190Singh 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.
- Background: PubMed 22607822Cholesterol 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.
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- Background: PubMed 23612326Perk 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.
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- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Flemming Dela, MD, MDSci principal investigator
University of Copenhagen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Training+Simvastatin+Q10 in people with Cardiovascular Disease and Diabetes Mellitus, run by University of Copenhagen at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 11 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Physical performance measured by VO2-max (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02796378, which also lists 13 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Feb 2021.