Exercise Intensity and Muscle Recovery in Statin Users (STN-EX)

April 25, 2026 updated by: Raffaele Mazzolari

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Statin-users (STN)
stable statin therapy ≥8 weeks
Other: Dose-Escalation Exercise Protocol
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.
Active Comparator: Statin-naïve controls (CON)
matched to STN
Other: Dose-Escalation Exercise Protocol
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in serum CK level from pre-exercise to 24 hours post-exercise
Time Frame: Baseline and 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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in PPT from pre-exercise to 24 hours post-exercise
Time Frame: Baseline and 24 hours post-exercise
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.
Baseline and 24 hours post-exercise
HR during Exercise
Time Frame: Continuous during each exercise session (from the start to the end of each endurance and resistance training session).
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.
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
Time Frame: Before the start and immediately after each endurance and resistance training session.
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.
Before the start and immediately after each endurance and resistance training session.
Subjective Need for Recovery after exercise (questionnaire)
Time Frame: Questionnaires will be collected daily to enable intra-individual robust scaling. However, the analysis will focus on recovery needs 24 hours post-exercise.
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.
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
Time Frame: RPE will be measured 10 minutes after the end of each endurance and resistance training session.
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.
RPE will be measured 10 minutes after the end of each endurance and resistance training session.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Raffaele Mazzolari

Collaborators

Universitaet Innsbruck

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

April 20, 2026

Primary Completion (Estimated)

June 1, 2027

Study Completion (Estimated)

June 1, 2027

Study Registration Dates

First Submitted

April 17, 2026

First Submitted That Met QC Criteria

April 25, 2026

First Posted (Actual)

May 4, 2026

Study Record Updates

Last Update Posted (Actual)

May 4, 2026

Last Update Submitted That Met QC Criteria

April 25, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1098/2025

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

Rendered code will be shared, and IPD data might not be available due to privacy constraints.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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