Exercise Intensity and Muscle Recovery in Statin Users (STN-EX)
Investigating the Role of Mechanical Muscle Loading in the Context of Preventive Exercise for Statin Users - a Pilot Study
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.
A tanulmány áttekintése
Állapot
Körülmények
Beavatkozás / kezelés
Részletes leírás
Study Design This is a matched-pairs, non-randomized, dose-escalation exercise trial with within-subject replication. Statin users (STN) and statin-naïve controls (CON) are matched by sex, age (±2 years), and body mass index (BMI) (±2 kg/m²). Due to ethical and safety reasons (risk of injury in untrained individuals exposed to high-intensity resistance exercise), the order of experimental periods is fixed: all participants begin with endurance exercise (lowest muscle strain), then progress to resistance training at 40%, 60%, and 80% of e1RM.
Interventions Endurance training sessions (END): 40 minutes cycling at 60% heart rate reserve (HRR), plus 5 min warm-up and cool-down.
Resistance training sessions (RT1-RT3): 8 machine-based exercises (e.g., leg press, chest press, lat pull-down). Two sets per exercise, repetitions decrease with intensity (20 reps at 40% e1RM, 12 reps at 60%, 8 reps at 80%). Rest between sets ~120 sec. Each intensity period includes two identical sessions, separated by a 5-21-day washout.
Procedures Screening: Medical history, physical exam, resting electrocardiogram (ECG), cardiopulmonary exercise test (CPET).
Baseline: Two measurements of CK from capillary blood and pressure pain threshold (PPT) on the rectus femoris.
Familiarization: Two low-intensity RT sessions to teach correct technique and breathing.
10-repetition maximum (10RM) testing: For each RT exercise, participants perform up to three attempts to find the maximal load for 10 controlled repetitions; then e1RM is calculated for intensity prescription.
Experimental periods: Each exercise session is preceded by a pre-exercise capillary CK sample and PPT assessment. Participants return 24h later for post-exercise CK and PPT. Before, during and/or immediately after exercise, heart rate (HR) and blood lactate are recorded. The rating of perceived exertion (RPE) is recorded 10 minutes after exercise. Daily online monitoring of muscle symptoms and recovery needs is performed throughout the study.
Outcome Measures Primary: Change in serum CK from pre- to 24h post-exercise (ΔCK).
Secondary: Change in PPT from pre- to 24h post-exercise (ΔPPT), change in blood lactate pre- to post-exercise, average HR during exercise, session-RPE, subjective recovery need (questionnaire) 24 hours after exercise.
Target Sample Size 40 participants (20 per group).
Statistical Analysis Linear mixed model with fixed effects: medication (statin vs. control), exercise intensity (END, RT1, RT2, RT3), and their interaction (main research question). Pre-exercise values as covariates; random intercept for subject. No time trend included as focus is on acute responses.
Ethics and Data Management All procedures follow preventive exercise guidelines. Participants benefit from supervised training and receive post-study exercise recommendations. Data are pseudonymized, stored within the European Union, and GDPR-compliant. Capillary sampling from the earlobe minimizes risks (only minor swelling/bruising possible).
Study Duration Total data acquisition <15 months; experimental phase per participant <4 months.
Tanulmány típusa
Beiratkozás (Becsült)
Fázis
- Nem alkalmazható
Kapcsolatok és helyek
Tanulmányi kapcsolat
- Név: Raffaele Mazzolari, Dr.
- Telefonszám: +393468754234
- E-mail: raffaele.mazzolari@i-med.ac.at
Tanulmányi helyek
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Tyrol
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Innsbruck, Tyrol, Ausztria, 6020
- Toborzás
- University of Innsbruck
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Kapcsolatba lépni:
- Raffaele Mazzolari, Dr.
- Telefonszám: +393468754234
- E-mail: raffaele.mazzolari@i-med.ac.at
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Részvételi kritériumok
Jogosultsági kritériumok
Tanulmányozható életkorok
- Felnőtt
- Idősebb felnőtt
Egészséges önkénteseket fogad
Leírás
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Tanulási terv
Hogyan készül a tanulmány?
Tervezési részletek
- Elsődleges cél: Alapvető tudomány
- Kiosztás: Nem véletlenszerű
- Beavatkozó modell: Párhuzamos hozzárendelés
- Maszkolás: Nincs (Open Label)
Fegyverek és beavatkozások
Résztvevő csoport / kar |
Beavatkozás / kezelés |
|---|---|
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Kísérleti: Statin-users (STN)
stable statin therapy ≥8 weeks
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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.
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Aktív összehasonlító: Statin-naïve controls (CON)
matched to STN
|
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.
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Mit mér a tanulmány?
Elsődleges eredményintézkedések
Eredménymérő |
Intézkedés leírása |
Időkeret |
|---|---|---|
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Change in serum creatine kinase (CK) level from pre-exercise to 24 hours post-exercise
Időkeret: Baseline and 24 hours post-exercise
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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.
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Baseline and 24 hours post-exercise
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Másodlagos eredményintézkedések
Eredménymérő |
Intézkedés leírása |
Időkeret |
|---|---|---|
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Blood lactate concentration before and after exercise
Időkeret: Before the start and immediately after each endurance and resistance training session.
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Blood lactate concentration will be measured from capillary blood samples drawn from the earlobe before and after each exercise session.
The outcome is the change from the pre-exercise baseline value to the value obtained immediately after each exercise session.
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Before the start and immediately after each endurance and resistance training session.
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Subjective Need for Recovery after exercise (questionnaire)
Időkeret: Questionnaires will be collected daily to enable intra-individual robust scaling. However, the analysis will focus on recovery needs 24 hours post-exercise.
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Subjective sensation of the need for recovery will be quantified using a validated questionnaire.
The specific questionnaire and its scoring range (minimum and maximum values) will be entered in the results reporting phase.
Higher scores indicate a greater need for recovery.
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Questionnaires will be collected daily to enable intra-individual robust scaling. However, the analysis will focus on recovery needs 24 hours post-exercise.
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Change in pressure pain threshold (PPT) from pre-exercise to 24 hours post-exercise
Időkeret: Baseline and 24 hours post-exercise
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PPT will be measured using a handheld algometer with a 1-cm² probe on the rectus femoris.
The outcome is the change from the pre-exercise baseline value to the value obtained 24 hours after each exercise session.
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Baseline and 24 hours post-exercise
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Heart rate (HR) during exercise
Időkeret: Continuous during each exercise session (from the start to the end of each endurance and resistance training session).
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HR will be measured continuously in beats per minute during the entire exercise session.
The outcome measure will be the average heart rate sustained over the duration of the session.
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Continuous during each exercise session (from the start to the end of each endurance and resistance training session).
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Session rating of perceived exertion (RPE)
Időkeret: RPE will be measured 10 minutes after the end of each endurance and resistance training session.
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Participants will rate their overall RPE for the entire exercise session using the Borg CR-10 scale.
Scores range from 0 (no exertion at all) to 10 (maximal exertion).
Session-RPE will be calculated by multiplying the RPE score by the duration of each exercise session.
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RPE will be measured 10 minutes after the end of each endurance and resistance training session.
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Együttműködők és nyomozók
Szponzor
Együttműködők
Publikációk és hasznos linkek
Általános kiadványok
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Tanulmányi rekorddátumok
Tanulmány főbb dátumok
Tanulmány kezdete (Tényleges)
Elsődleges befejezés (Becsült)
A tanulmány befejezése (Becsült)
Tanulmányi regisztráció dátumai
Először benyújtva
Először nyújtották be, amely megfelel a minőségbiztosítási kritériumoknak
Első közzététel (Tényleges)
Tanulmányi rekordok frissítései
Utolsó frissítés közzétéve (Tényleges)
Az utolsó frissítés elküldve, amely megfelel a minőségbiztosítási kritériumoknak
Utolsó ellenőrzés
Több információ
A tanulmányhoz kapcsolódó kifejezések
Kulcsszavak
További vonatkozó MeSH feltételek
Egyéb vizsgálati azonosító számok
- 1098/2025
Terv az egyéni résztvevői adatokhoz (IPD)
Tervezi megosztani az egyéni résztvevői adatokat (IPD)?
IPD terv leírása
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