CHANges iN skEletal muscLe in Heart Failure (Channel-HF)

Changes in Skeletal Muscle Over Time in Severe Heart Failure

The mechanisms behind heart failure are largely unknown. Despite an increasing arsenal of pharmacological therapies, cardiovascular disease is still the most common cause of death in the western world, which demonstrates a pronounced need for more patient-related mechanistic research. Cachexia and limited exercise capacity are the symptoms that best match prediction of heart failure, both of which are symptoms involving a dysfunctional skeletal muscle. An increased understanding of the mechanisms and signaling pathways connects the failure heart with skeletal muscle dysfunction is likely to lead both to discoveries of prognostic factors and possible therapeutic options.

The study is a prospective, non-blinded, study. The study will consist of the assignment of patients with heart failure, New York Heart Association (NYHA) III-IV, 60-80 years old. One hundred (100) patients will be enrolled in this study.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure

Detailed Description

The primary objective is to investigate how changes in the skeletal muscle coincide with changes in physical performance, cardiac function, and prognosis in patients with heart failure, and changes over time. Therefore, the investigators will investigate patients with severe heart failure at 'baseline' and on a second follow-up occasion after 12-16 months.

The secondary and tertiary objective is to investigate how changes in the metabolic signature of blood and satellite cells coincide with changes in physical performance, cardiac function, and prognosis in patients with heart failure, and changes over time. Patient recruitment is expected to occur over 36 months.

The study will be conducted in Sweden at Karolinska University Hospital, Huddinge.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Thomas Gustafsson, MD, PhD; Phone Number: +46707415124; Email: thomas.gustafsson@ki.se
• Study Contact Backup: Name: Eric Rullman, MD, PhD; Phone Number: +46739708096; Email: eric.rullman@ki.se

Study Locations

• Sweden
  • Stockholms Län
    • Stockholm, Stockholms Län, Sweden, 144 86
      • Recruiting
      • Karolinska University Hospital
      • Contact: Michael Melin, MD; Phone Number: #46723888636; Email: michael.melin@sll.se
      • Contact: Eric Rullman, MD, PhD; Phone Number: #46739708096; Email: eric.rullman@ki.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with severe heart failure

Description

Inclusion criteria:

• Signed informed consent
• 60-80 years old upon inclusion
• Chronic heart failure ≥ 45 days.
• Left ventricular ejection fraction ≤ 35%.
• NYHA III-IV
• Receiving medical management with optimal doses of betablockers, acetylcholinesterase (ACE)-inhibitors or angiotensin II receptor blockers (ARB), and mineral receptor antagonists (MRA) for at least 30 days if tolerated.

Exclusion criteria:

• Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile 1 "crash and burn"
• On-going mechanical circulatory support.
• Severe chronic obstructive pulmonary disease (COPD) or severe restrictive lung disease.
• Psychiatric disease, cognitive dysfunction, alcohol or drug abuse, or psychosocial issues that are likely to impair study compliance
• Condition, other than heart failure, requiring end-of-life care within <6 months in time or where the risk of death within <2 years is considered to be imminent.
• Participation in studies that resulted in departure from normal treatment routine or invasive investigations within <6 months back in time.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metabolic signature of muscle, messenger RNA (mRNA) gene expression	Metabolomics profile using nuclear magnetic resonance (NMR)	Change from baseline metabolic signature at 24 months
Metabolic signature of muscle, messenger RNA (mRNA) gene	Metabolomics profile using liquid chromatography-high-resolution mass spectrometry (LC-HRMS)	Change from baseline metabolic signature at 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metabolic signature of blood, mRNA gene expression	Metabolomics profile using NMR	Change from baseline metabolic signature at 24 months
Metabolic signature of blood, mRNA gene expression	Metabolomics profile using LC-HRMS	Change from baseline metabolic signature at 24 months
Metabolic signature of satellite cells, mRNA gene expression	Metabolomics profile using NMR	Change from baseline metabolic signature at 24 months
Metabolic signature of satellite cells, mRNA gene expression	Metabolomics profile using LC-HRMS	Change from baseline metabolic signature at 24 months
Expression levels of targeted genes using transcriptomics	Choice of genes based on results obtained by metabolomics approaches	Change from baseline metabolic signature at 24 months

Collaborators and Investigators

• Sponsor: Karolinska Institutet
• Collaborators: Region Stockholm
• Investigators: Study Chair: Matti Sällberg, professor, Karolinska Institutet

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2018
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2025

Study Registration Dates

• First Submitted: November 20, 2017
• First Submitted That Met QC Criteria: January 8, 2018
• First Posted (Actual): January 17, 2018

Study Record Updates

• Last Update Posted (Actual): October 6, 2020
• Last Update Submitted That Met QC Criteria: October 4, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Heart failure; Lung function; Gene expression; Skeletal muscle; Exercise capacity
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: Channel-HF KI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No