Mangafodipir - an Intracellular Contrast Agent for Magnetic Resonance Imaging (MRI): Measuring Manganese Uptake Rate in Heart Failure Patients With Preserved Ejection Fraction (HFpEF) Patients.

NCT06731738 | Completed Phase 2

• 2 other identifiers: MNC0012023-508118-40-01
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

More than half of heart failure patients have preserved ejection fraction (HFpEF), a condition caused by increased wall stiffness that impairs proper heart filling. Two types of cardiac fibrosis, replacement fibrosis and interstitial fibrosis, contribute to this stiffening. In addition, altered calcium handling in the cardiomyocytes is relevant. The currently available contrast agents in Magnetic Resonace Imaging (MRI) primarily detect cell loss caused by replacement fibrosis, and measurements of the extracellular volume provide clues about the status of interstitial fibrosis. However, the planned trial aims to utilise mangafodipir trisodium to measure cellular function independent of the impact of fibrosis. This information could be vital for accurate diagnosis, selection and monitoring of therapy. In addition, manganese-enhanced magnetic resonance imaging (MEMRI) may be used as an alternative to examinations with gadolinium-based contrast agents in the future.

Conditions

Heart Failure With Preserved Ejection Fraction (HFPEF)

Keywords

Mangafodipir; HFpEF; CMR; Heart Failure; Heart Disease; Manganese-enhanced magnetic resonance imaging (MEMRI)

Outcome Measures

Primary Outcomes (1)

• To quantify the manganese uptake rate after administration of mangafodipir trisodium in all segments of the left ventricular wall.

  Determination of the manganese uptake rate.

  Images to be captured during the trial MRI examinations (up to 60 to 90 minutes after the drug administration); image evaluations shall be executed remotely.

Secondary Outcomes (5)

• Efficacy: Comparison of manganese uptake rate constant in healthy volunteers, HFpEF with HCM or CA.

  Images to be captured during the trial MRI examinations (up to 60 to 90 minutes after the drug administration); image evaluations shall be executed remotely.

• To assess the safety of mangafodipir trisodium injection based on AEs.

  From AMP administration at Visit 2 to the end of the Follow-up period (1 day after Vist 3).

• To assess the safety of mangafodipir trisodium injection based on injection site AEs.

  From AMP administration at Visit 2 to the end of the Follow-up period (1 day after Vist 3).

• To assess the safety of mangafodipir trisodium injection based on vital signs.

  From AMP administration at Visit 2 to the end of the Follow-up period (1 day after Vist 3).

• To assess the safety of mangafodipir trisodium injection based on ECG.

  From AMP administration at Visit 2 to the end of the Follow-up period (1 day after Vist 3).

Study Arms (3)

HFpEF with HCM

EXPERIMENTAL

Heart failure patients with preserved ejection fraction caused by hypertrophic cardiomyopathy. Participants will have 2 cardiac MRIs (gadolinium- and manganese-enhanced) at Visit 2 and Vist 3, respectively.

Drug: Gadoteric acid; Drug: Mangafodipir trisodium injection

HFpEF with CA

EXPERIMENTAL

Heart failure patients with preserved ejection fraction caused by cardiac amyloidosis. Participants will have 2 cardiac MRIs (gadolinium- and manganese-enhanced) at Visit 2 and Vist 3, respectively.

Drug: Gadoteric acid; Drug: Mangafodipir trisodium injection

Healthy Volunteers

EXPERIMENTAL

Participants will have 2 cardiac MRIs (gadolinium- and manganese-enhanced) at Visit 2 and Vist 3, respectively.

Drug: Gadoteric acid; Drug: Mangafodipir trisodium injection

Interventions

Gadoteric acid DRUG

A gadolinium-based contrast agent (authorised auxiliary medicinal product (AMP)) will be injected i.v. at a dose of 0.2 mmol Gd/kg bw and T1 mapping and ECV measurement will be done.

HFpEF with CA; HFpEF with HCM; Healthy Volunteers

Mangafodipir trisodium injection DRUG

Mangafodipir trisodium injection (IMP) will be administered i.v. at a dose of 5 µmol/kg bw and T1 mapping, Saturation Recovery T1 weighted imaging for measurement of the uptake rate, and T2 mapping, will be done.

HFpEF with CA; HFpEF with HCM; Healthy Volunteers

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants who have given their signed declaration of consent and data protection declaration.
• Males and females (postmenopausal or surgically sterile females) aged ≥ 18 years and ≤ 90 years
• HFpEF (= LVEF \> 50%) with NYHA (New York Heart Association) class I, II and III and objective evidence of cardial structural and/or functional abnormalities consistent with the presence of left ventricular (LV) diastolic dysfunction/raised LV filling pressures, including raised natriuretic peptides.
• Patients with HCM or CA (according to current guidelines)
• Kidney functions eGFR (Estimated Glomerular Filtration Rate) \> 30 mL/min/1.73 m2
• Healthy volunteers (cohort specific criteria): adults with no known pre-existing medical conditions.

You may not qualify if:

• Tachycardia (heart rate \> 100, R-R interval \< 600 ms)
• NYHA IV
• Previous coronary artery disease requiring intervention, including history of myocardial infarction including septal reduction therapies
• Severely reduced renal function, defined as eGFR \< 30 mL/min/1.73 m2
• Severely reduced liver function (Child-Pugh class C), especially severe obstructive hepatobiliary disease
• Phaeochromocytoma
• Advanced cancer (with short/medium term prognosis)
• History of chest radiation therapy
• Diabetic patients
• Severe valvular disease
• Previous heart surgery
• Left ventricular assist device (LVAD)
• Severe pulmonary disease
• Hypersensitivity to any medicinal products containing gadolinium
• Hypersensitivity to the active substance of the IMP or to any of the excipients

Sponsors & Collaborators

• IC TARGETS AS: lead

Study Sites (1)

Oslo University Hospital, Department of Cardiology, Rikshospitalet Sognsvannsveien 20

Oslo, Oslo County, 0372, Norway

Location

MeSH Terms

Conditions

Heart Failure; Heart Diseases

Interventions

N,N'-bis(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid

Condition Hierarchy (Ancestors)

Cardiovascular Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2024
• First Posted: December 12, 2024
• Study Start: November 22, 2024
• Primary Completion: November 29, 2025
• Study Completion: November 29, 2025
• Last Updated: January 8, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

NO (1)