Exercise Intensity and Muscle Recovery in Statin Users

NCT07563452 | Recruiting

• 1 other identifier: 1098/2025
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to investigate how different types and intensities of exercise affect muscle recovery in individuals taking statin medications compared to healthy controls. Statins are essential for cardiovascular prevention but are often associated with muscle-related side effects (SAMS), which can be exacerbated by physical activity. The study will compare aerobic cycling (low muscular strain) with resistance training (RT) at increasing intensities (40%, 60%, and 80% of estimated 1-repetition maximum; e1RM). Researchers will measure markers of muscle damage, such as creatine kinase (CK) levels, and subjective recovery needs to determine which exercise modalities and intensities are best tolerated by statin users. The goal is to provide evidence for more individualized and safer exercise recommendations for this population.

Conditions

Statin Adverse Reaction

Keywords

Statin; Statin-associated muscle symptoms; SAMS; Resistance training; Endurance training; Muscle loading; Creatine kinase; Recovery need; Exercise intensity

Outcome Measures

Primary Outcomes (1)

• Change in serum CK level from pre-exercise to 24 hours post-exercise

  Serum CK will be measured from capillary blood samples drawn from the earlobe. The outcome measure is the calculated change from the pre-exercise baseline value to the value obtained 24 hours after each exercise session.

  Baseline and 24 hours post-exercise

Secondary Outcomes (5)

• Change in PPT from pre-exercise to 24 hours post-exercise

  Baseline and 24 hours post-exercise

• HR during Exercise

  Continuous during each exercise session (from the start to the end of each endurance and resistance training session).

• Blood lactate concentration before and after exercise

  Before the start and immediately after each endurance and resistance training session.

• Subjective Need for Recovery after exercise (questionnaire)

  Questionnaires will be collected daily to enable intra-individual robust scaling. However, the analysis will focus on recovery needs 24 hours post-exercise.

• Session-RPE

  RPE will be measured 10 minutes after the end of each endurance and resistance training session.

Study Arms (2)

Statin-users (STN)

EXPERIMENTAL

stable statin therapy ≥8 weeks

Other: Dose-Escalation Exercise Protocol

Statin-naïve controls (CON)

ACTIVE COMPARATOR

matched to STN

Other: Dose-Escalation Exercise Protocol

Interventions

Dose-Escalation Exercise Protocol OTHER

A dose-escalation protocol consisting of END (40 minutes of cycling at 60% HRR) and RT at 40%, 60%, and 80% of e1RM. RT includes 8 machine-based exercises, 2 sets per exercise, with repetitions decreasing as intensity increases (20, 12, and 8 reps respectively). Each intensity period comprises two identical sessions with a 5-21 day washout. All sessions are supervised.

Statin-naïve controls (CON); Statin-users (STN)

Eligibility Criteria

• Age: 30 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Sedentary behavior (defined as \< 1 hour of planned physical activity per week)
• Low occupational physical activity
• Age between 30 and 65 years
• Non-smoker
• Medical clearance to partake in physical exercise (as determined during screening visit)
• For statin users: Current statin medication with stable dosage for at least 8 weeks prior to enrollment
• For controls: Statin-naïve individuals

You may not qualify if:

• BMI \< 20 kg/m² or \> 30 kg/m²
• Smoking or smoking cessation \< 1 year ago
• Medical conditions or musculoskeletal issues that preclude eligibility for full physical effort or interfere with outcome measures
• Medication (other than statins) that may interfere with physical exercise or outcome measures (assessment on a case-by-case basis during screening visit)
• Any condition identified during screening (e.g., abnormal ECG, cardiopulmonary exercise test) that, in the opinion of the physician, precludes safe participation

Sponsors & Collaborators

• Raffaele Mazzolari: lead
• Universitaet Innsbruck: collaborator

Study Sites (1)

University of Innsbruck

Innsbruck, Tyrol, 6020, Austria

RECRUITING

Related Publications (11)

• Ruscica M, Ferri N, Banach M, Sirtori CR, Corsini A. Side effects of statins: from pathophysiology and epidemiology to diagnostic and therapeutic implications. Cardiovasc Res. 2023 Jan 18;118(17):3288-3304. doi: 10.1093/cvr/cvac020.

  PMID: 35238338 BACKGROUND

• Sinzinger H, O'Grady J. Professional athletes suffering from familial hypercholesterolaemia rarely tolerate statin treatment because of muscular problems. Br J Clin Pharmacol. 2004 Apr;57(4):525-8. doi: 10.1111/j.1365-2125.2003.02044.x.

  PMID: 15025753 BACKGROUND

• Hoppstadter J, Valbuena Perez JV, Linnenberger R, Dahlem C, Legroux TM, Hecksteden A, Tse WKF, Flamini S, Andreas A, Herrmann J, Herr C, Muller R, Meyer T, Bals R, Riccardi C, Bruscoli S, Kiemer AK. The glucocorticoid-induced leucine zipper mediates statin-induced muscle damage. FASEB J. 2020 Mar;34(3):4684-4701. doi: 10.1096/fj.201902557RRR. Epub 2020 Feb 6.

  PMID: 32030813 BACKGROUND

• Hecksteden A, Hoppstadter J, Bizjak DA, Jerg A, Kirsten J, Kruger K, Niess A, Steinacker J, Kiemer AK. Effects of acute exercise and training status on glucocorticoid-induced leucine zipper (GILZ) expression in human skeletal muscle. J Sci Med Sport. 2023 Dec;26(12):707-710. doi: 10.1016/j.jsams.2023.10.007. Epub 2023 Oct 21.

  PMID: 37951824 BACKGROUND

• Paul S, Donath L, Hoppstadter J, Hecksteden A. Resistance but not endurance training suppresses glucocorticoid-induced leucine zipper (GILZ) expression in human skeletal muscle. Eur J Appl Physiol. 2025 Apr;125(4):1023-1036. doi: 10.1007/s00421-024-05644-7. Epub 2024 Nov 5.

  PMID: 39499305 BACKGROUND

• Morales-Palomo F, Ramirez-Jimenez M, Ortega JF, Moreno-Cabanas A, Mora-Rodriguez R. Exercise Training Adaptations in Metabolic Syndrome Individuals on Chronic Statin Treatment. J Clin Endocrinol Metab. 2020 Apr 1;105(4):dgz304. doi: 10.1210/clinem/dgz304.

  PMID: 31875915 BACKGROUND

• Stroes ES, Thompson PD, Corsini A, Vladutiu GD, Raal FJ, Ray KK, Roden M, Stein E, Tokgozoglu L, Nordestgaard BG, Bruckert E, De Backer G, Krauss RM, Laufs U, Santos RD, Hegele RA, Hovingh GK, Leiter LA, Mach F, Marz W, Newman CB, Wiklund O, Jacobson TA, Catapano AL, Chapman MJ, Ginsberg HN; European Atherosclerosis Society Consensus Panel. Statin-associated muscle symptoms: impact on statin therapy-European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management. Eur Heart J. 2015 May 1;36(17):1012-22. doi: 10.1093/eurheartj/ehv043. Epub 2015 Feb 18.

  PMID: 25694464 BACKGROUND

• Mikus CR, Boyle LJ, Borengasser SJ, Oberlin DJ, Naples SP, Fletcher J, Meers GM, Ruebel M, Laughlin MH, Dellsperger KC, Fadel PJ, Thyfault JP. Simvastatin impairs exercise training adaptations. J Am Coll Cardiol. 2013 Aug 20;62(8):709-14. doi: 10.1016/j.jacc.2013.02.074. Epub 2013 Apr 10.

  PMID: 23583255 BACKGROUND

• Parker BA, Augeri AL, Capizzi JA, Ballard KD, Troyanos C, Baggish AL, D'Hemecourt PA, Thompson PD. Effect of statins on creatine kinase levels before and after a marathon run. Am J Cardiol. 2012 Jan 15;109(2):282-7. doi: 10.1016/j.amjcard.2011.08.045. Epub 2011 Oct 28.

  PMID: 22036108 BACKGROUND

• Kearns AK, Bilbie CL, Clarkson PM, White CM, Sewright KA, O'Fallon KS, Gadarla M, Thompson PD. The creatine kinase response to eccentric exercise with atorvastatin 10 mg or 80 mg. Atherosclerosis. 2008 Sep;200(1):121-5. doi: 10.1016/j.atherosclerosis.2007.12.029. Epub 2008 Feb 7.

  PMID: 18261731 BACKGROUND

• Laufs U, Filipiak KJ, Gouni-Berthold I, Catapano AL; SAMS expert working group. Practical aspects in the management of statin-associated muscle symptoms (SAMS). Atheroscler Suppl. 2017 Apr;26:45-55. doi: 10.1016/S1567-5688(17)30024-7.

  PMID: 28434484 BACKGROUND

MeSH Terms

Conditions

Short Stature, Auditory Canal Atresia, Mandibular Hypoplasia, Skeletal Abnormalities

Central Study Contacts

Raffaele Mazzolari, Dr.

CONTACT

+393468754234; raffaele.mazzolari@i-med.ac.at

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: PostDoc, Principal Investigator

Model Details: Participants are assigned to two parallel groups: STN and CON. CON are matched to STN by sex, age (±2 years), and BMI (±2 kg/m²). Allocation is non-randomized due to the nature of the exposure (statin medication status). Both groups undergo the same four acute exercise periods with dose escalation (END, RT1, RT2, RT3), each replicated twice, with a 5-21 day wash-out between sessions. Fixed order (non-randomized) for ethical/safety reasons; familiarization and intermittent strength testing calibrate intensity.

Study Record Dates

• First Submitted: April 17, 2026
• First Posted: May 4, 2026
• Study Start: April 20, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: May 4, 2026

Record last verified: 2026-04

Locations

AU (1)