Digoxin and Senolysis in Heart Failure and Diabetes Mellitus

NCT06240403 | Not Yet Recruiting Phase 2

• 1 other identifier: 339442
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

In pilot studies the investigators have shown that subcutaneous adipose tissue (SAT) from patients with reduced ejection fraction heart failure (HFrEF) and type 2 diabetes mellitus (T2DM) is dysfunctional. Endothelial cells from the adipose tissue from these patients are senescent and have deleterious effects on healthy human subcutaneous adipocytes, including increasing expression of IL-6 (gene and protein) and reducing glucose uptake. Digoxin, a well-established treatment for HFrEF, selectively clears these senescent endothelial cells and prevents adipocyte dysfunction. This study will examine the effect of digoxin on adipose tissue on the burden of senescent cells.

Conditions

Heart Failure, Systolic; Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (1)

• SAT microvascular endothelial cell β-galactosidase

  Change in MVEC senescence associated β-galactosidase expression in cultured MVEC will be assessed using CellEvent Senescence Green Detection Kit in fat biopsies.

  Three months

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Two capsules of placebo taken orally per day for three months

Drug: Digoxin 0.125 MG

Digoxin

EXPERIMENTAL

Two capsules containing 62.5mcg digoxin taken orally per day for three months

Drug: Digoxin 0.125 MG

Interventions

Digoxin 0.125 MG DRUG

One capsule containing digoxin per day for three months

Digoxin; Placebo

Eligibility Criteria

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

You may qualify if:

• Aged ≥18yrs,
• HFrEF (LVEF\<40%)
• T2DM (taking anti-diabetic medication, fasting plasma glucose ≥7.0 mmol/L and/or a serum HbA1c \>48mmol/L
• On optimal medical therapy,
• Able/prepared to give informed written consent.

You may not qualify if:

• Significant cognitive impairment,
• Important co-morbidity limiting ability to comply with study procedures,
• Hyperkalemia (\>5.5mmol/L)
• eGFR\<30ml/min/1.73m2
• Current/previous (\<6m) participation in other studies.

Sponsors & Collaborators

• University of Leeds: lead

Study Sites (1)

Leeds Teaching Hospitals NHS Trust

Leeds, West Yorkshire, LS16 5AR, United Kingdom

Location

MeSH Terms

Conditions

Heart Failure, Systolic; Diabetes Mellitus, Type 2

Interventions

Digoxin

Condition Hierarchy (Ancestors)

Heart Failure; Heart Diseases; Cardiovascular Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates

Central Study Contacts

Klaus Witte

CONTACT

00447768254073; k.k.witte@leeds.ac.uk

Mark Kearney

CONTACT

00447768254073; m.t.kearney@leeds.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants will take either digoxin or placebo.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Lecturer in Cardiology

Study Record Dates

• First Submitted: January 23, 2024
• First Posted: February 5, 2024
• Study Start: September 1, 2025
• Primary Completion (Estimated): August 28, 2028
• Study Completion (Estimated): August 28, 2029
• Last Updated: December 6, 2024

Record last verified: 2024-12

Locations

GB (1)