Effect of Weight Loss on Physical and Cardiac Performance in People With Obesity and Heart Failure

NCT06423599 | Recruiting Phase 2 DMC

• 2 other identifiers: U1111-1298-64182023-503753-35-01
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The benefit of weight loss in patients with obesity and heart failure with reduced ejection fraction (HFrEF) is controversial. Semaglutide has shown cardiovascular (CV) risk-reduction and impact on CV risk factors including overweight, dysglycaemia and hypertension in subjects with type 2 diabetes (T2D). The STEP-HFpEF (Semaglutide Treatment Effect in People With Obesity and HFpEF) recently demonstrated, at 1-year, to not only reduce weight considerably, but also significantly improve health-related quality of life, functional status scores and 6-min walk distance in patients with heart failure with preserved ejection fraction (HFpEF). Also, the recently concluded SELECT trial was the first CV outcome trial with semaglutide in patients with overweight or obesity and established CV disease, including heart failure (but no T2D). Semaglutide demonstrated a 20% reduction in MACE, defined as the composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. These landmark findings have important implications for clinicians -as they mean that weight loss and/or semaglutide as anti-obesity pharmacotherapy could be a treatment strategy for secondary prevention of CV disease in patients with overweight or obesity. It is, however, unknown whether weight loss with either calorie-restricted diet or semaglutide has beneficial effects in obese subjects with heart failure and reduced ejection fraction. Also it is unclear whether semaglutide has cardiovascular benefits irrespective of starting weight and amount of weight loss. Purpose: The study aims to investigate whether weight loss treatment with semaglutide is superior to weight loss with calorie-restricted diet in improving peak oxygen uptake in patients with obesity and heart failure with reduced ejection fraction.

Conditions

Heart Failure With Reduced Ejection Fraction; Obesity; Weight Loss; Chronic Heart Failure

Outcome Measures

Primary Outcomes (1)

• Peak oxygen uptake

  To examine the effect of weight loss on mean change in peak oxygen uptake at 52 weeks between semaglutide and calorie-restricted group compared to baseline (Measured in ml O2/(kg x min))

  The patients will be examined after 0, 16 and 52 weeks

Secondary Outcomes (4)

• The Clinical Summary Score of the Kansas City Cardiomyopathy Questionnaire (KCCQ-CSS)

  The patients will be examined after 0, 16 and 52 weeks.

• 6-min walk distance (6MWD)

  The patients will be examined after 0, 16 and 52 weeks

• End-systolic volume of the left ventricle assessed by Cardiac MRI

  The patients will be examined after 0, 16 and 52 weeks

• N-terminal pro-B-type natriuretic peptide (NT-proBNP) and C-reactive protein (CRP) change

  The patients will be examined after 0, 16 and 52 weeks

Other Outcomes (12)

• Composite endpoint consisting of all-cause death, non-fatal myocardial infarction, non-fatal stroke, heart failure hospitalisation or urgent heart failure visit

  Follow-up at 52 weeks

• First occurrence of a composite heart failure endpoint consisting of: heart failure hospitalisation, urgent heart failure visit, ischemic events or CV death

  Follow-up at 52 weeks

• All-cause death

  Follow-up at 52 weeks

Study Arms (2)

Semaglutide intervention group

EXPERIMENTAL

Dose-escalation of semaglutide will take place during the first 16 weeks after randomisation (week 0). Patients will start at the 0.25 mg once-weekly dose and follow dose-escalation schedule (0.25, 0.5, 1.0, 1.7 and 2.4 mg). For all subjects we aim at reaching the recommended target dose of 2.4 mg semaglutide once weekly for the rest of the period of total 52 weeks.

Drug: Semaglutide Injectable Product

Calorie-restricted diet intervention group

ACTIVE COMPARATOR

In short, the weight loss program in the calorie-restricted diet group consists of 3 phases after randomisation (week 0). An initial weight loss phase of 8 weeks with 800 calories/day, a food re-introduction phase for 8 weeks and a weight loss maintenance phase for the rest of the period of total 52 weeks.

Dietary Supplement: Calorie-restricted diet

Interventions

Semaglutide Injectable Product DRUG

Weight loss using Semaglutide

Semaglutide intervention group

Calorie-restricted diet DIETARY_SUPPLEMENT

Weight loss by calorie-restricted diet program followed by a weight loss maintenance follow-up program

Calorie-restricted diet intervention group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, age ≥ 18 years at the time of signing informed consent
• Body mass index (BMI) ≥ 30 kg/m2
• Heart failure with New York Heart Association (NYHA)-class 1-3 and reduced ejection fraction (EF≤40%) established by either:
• echocardiography AND/OR
• cardiac magnetic resonance
• On stable optimal medical heart failure therapy for at least 4 weeks

You may not qualify if:

• Cardiovascular-related:
• Any of the following: myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischaemic attack within the past 6 months prior to the day of screening
• Planned coronary, carotid or peripheral artery revascularisation known on the day of screening
• Transient heart failure related to reversible mechanisms like tachycardia, sepsis, etc.
• Glycaemia-related:
• Type 1 diabetes
• Treatment with any Glucagon-Like Peptide-1 (GLP-1) agonists within 90 days prior to the day of screening
• Type 2 diabetes requiring other pharmacotherapy than metformin and Sodium-glucose Cotransporter-2 (SGLT2) Inhibitors
• General safety:
• Pregnancy or planned pregnancy
• History or presence of chronic pancreatitis
• Presence of acute pancreatitis within the past 180 days prior to the day of screening
• Kidney disease with eGFR \< 35ml/min
• Presence or history of malignant neoplasms within the past 5 years prior to the day of screening (Basal and squamous cell skin cancer and any carcinoma in-situ are allowed)
• Known or suspected hypersensitivity to trial product(s) or related products

Sponsors & Collaborators

• Jens D Hove, MD,PHD: lead

Study Sites (1)

Amager and Hvidovre Hospital University of Copenhagen

Copenhagen, DK-2650, Denmark

RECRUITING

MeSH Terms

Conditions

Obesity; Weight Loss

Interventions

Caloric Restriction

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Body Weight Changes

Intervention Hierarchy (Ancestors)

Diet Therapy; Nutrition Therapy; Therapeutics; Energy Intake; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Jens D Hove

  Amager-Hvidovre Universitetshospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jens D Hove, MD, PhD

CONTACT

+4538623218; jens.dahlgaard.hove@regionh.dk

Mohammed El-Sheikh, MD

CONTACT

+4552309685; mohammed.el-sheikh.02@regionh.dk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Anonymized data will be analyzed
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief Physician, Research associate Professor, MD, PhD

Model Details: This is a investigator-initiated, parallel-group, 2-arm assessor-blinded, open-label, randomised, clinical trial

Study Record Dates

• First Submitted: May 16, 2024
• First Posted: May 21, 2024
• Study Start: May 17, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: May 24, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)