Mechanism of Sarcopenia in Heart Failure

Recruiting

• Conditions: Cachexia; Heart Failure; Sarcopenia

• Registration Number: NCT05063955
• Lead Sponsor: Aarhus University Hospital

Brief Summary

The aim of the study is to provide information on the interaction between socioeconomic factors, daily physical activity, nutrition and lifestyle on loss of muscle mass and muscle function in patients with heart failure.

Detailed Description

A total of 200 consecutive heart failure patients will be included and 50 age and sex-matched individuals with no history of cardiovascular disease will serve as controls.

Baseline variables of body composition, physical capacity, daily physical activity, nutritional status, quality of life, socioeconomic status and insulin resistance will be obtained along with a skeletal muscle tissue biopsy and blood samples for laboratory analyses.

Baseline variables from heart failure patients will be compared to healthy controls.

Patients and controls will be invited to follow-up visits at 12 and 36 months. Changes in baseline variables will be analyzed.

Events will be identified through national registries.

Study Timeline

• Study Start: 2020-12-02
• Study First Submitted: 2021-06-01
• Study First Submitted QC: 2021-09-28
• Study First Posted: 2021-10-01
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-19
• Last Update Posted: 2023-12-26
• Primary Completion: 2026-12-31
• Study Completion: 2033-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 250

Inclusion Criteria

1. Ability to provide valid informed consent.
2. Heart failure with preserved, mid-range or reduced ejection fraction (NYHA I-IV) according to European Society of Cardiology guidelines.

Exclusion Criteria

1. Cancer requiring treatment (e.g. prostate cancer on watchful waiting does not exclude patients).
2. Severe musculoskeletal or neurological disability.
3. Severe lung disease with a forced expiratory volume 1 < 40% of predicted. Treatment with anticoagulants (warfarin, apixaban, edoxaban, dabigatran and rivaroxaban) is an exclusion criterion for muscle biopsy. Patients with anticoagulant treatment will be invited to participate in the study without muscle biopsy.
4. Other comorbidities that prevent the patient from participating in the study examinations as judged by the investigator.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Physical performance, walking distance	From baseline to 12 and 36 months	Change in walking distance (6MWT) in meters
Physical performance, peak VO2	From baseline to 12 and 36 months	Change in peak oxygen uptake (peak VO2), measured in ml O2/kg/min
Physical performance, muscle strength	From baseline to 12 and 36 months	Change in knee extension/flexion isokinetic strength (assessed by peak torque, Nm) and isometric strength (assessed by peak torque, Nm)

Secondary Outcome Measures

Name	Time	Method
Body composition	From baseline to 12 and 36 months	Change in appendicular lean mass (measured in grams) and fat mass (measured in grams)
Daily physical activity	From baseline to 12 and 36 months	Change in daily physical activity assessed by 7-day accelerometry
Muscle tissue cellular composition	From baseline to 12 and 36 months	Change in muscle tissue cellular composition assessed by cell sorting
Whole body metabolism	From baseline to 12 and 36 months	Changes in circulating metabolic markers
Cardiovascular events	During follow-up of 10 years	Incidence of a composite endpoint of death, hospitalization with worsening of heart failure other cardiovascular events (myocardial infarction, unstable angina, revascularization and stroke) and non-cardiovascular hospitalizations
Insulin resistance	From baseline to 12 and 36 months	Changes in insulin resistance assessed by Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)
Muscle metabolism	From baseline to 12 and 36 months	Changes in metabolic signature of muscle tissue assessed by liquid chromatography-high-resolution mass spectrometry
Symptoms	From baseline to 12 and 36 months	Changes in the Minnesota Living with Heart Failure Questionnaire score (range 0-105, from best to worst)
Muscle tissue fiber types	From baseline to 12 and 36 months	Change in ratio between muscle fiber types (type I, IIa and IIb) assessed by immunohistochemistry
Muscle tissue mitochondrial function	From baseline to 12 and 36 months	Change in muscle mitochondrial function assessed by high-resolution respirometry

Trial Locations

Locations (1)

Aarhus University Hospital; 🇩🇰 Aarhus N, Denmark