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

NCT ID: NCT06731738

Last Updated: 2026-01-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-11-22
• Study Completion Date: 2025-11-29

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.

Detailed Description

The trial is an open-label, single centre, Phase 2A, Proof-of-Concept (PoC) trial in adult male and female patients without randomisation.

Overall, up to 42 participants will be enrolled in this trial:

• A run-in phase will include up to 6 participants (healthy volunteers and HFpEF patients regardless of aetiology (HCM, CA).
• The main phase of the trial will include 12 HFpEF with HCM, 12 HFpEF with CA and 12 healthy volunteers.

During a run-in phase up to 6 participants will be enrolled to standardise the trial procedures, especially mangafodipir-enhanced imaging.

The number and sequence of trial visits will be the same for participants of the run-in and the main phase.

All enrolled participants will undergo gadolinium-enhanced imaging at Visit 2. A gadolinium-based contrast agent (authorised AMP) will be injected i.v. and T1 mapping and Extracellular Volume (ECV) measurement will be done for approximately 60 minutes.

Mangafodipir-enhanced mapping will be done at Visit 3. After baseline T2 mapping, mangafodipir trisodium injection (IMP) will be administered i.v. and T1 mapping, Saturation Recovery T1 weighted imaging for measurement of the uptake rate, and T2 mapping, will be done for approximately 90 minutes.

Clinical safety data will be collected throughout the trial; the participants will be followed up by a phone call 24+6 hours after Visit 3 for evaluation of late-appearing AEs.

The analyses of the images will be done by an investigator of the study team, blinded to the clinical data.

Conditions

Heart Failure With Preserved Ejection Fraction (HFPEF)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

HFpEF with HCM

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.

Group Type: EXPERIMENTAL

Gadoteric acid

Intervention Type: 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.

Mangafodipir trisodium injection

Intervention Type: 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

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.

Group Type: EXPERIMENTAL

Gadoteric acid

Intervention Type: 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.

Mangafodipir trisodium injection

Intervention Type: 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.

Healthy Volunteers

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

Group Type: EXPERIMENTAL

Gadoteric acid

Intervention Type: 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.

Mangafodipir trisodium injection

Intervention Type: 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.

Interventions

Gadoteric acid

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.

Intervention Type: DRUG

Mangafodipir trisodium injection

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Participants who have given their signed declaration of consent and data protection declaration.

2. Males and females (postmenopausal or surgically sterile females) aged ≥ 18 years and ≤ 90 years

3. 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.

4. Patients with HCM or CA (according to current guidelines)

5. Kidney functions eGFR (Estimated Glomerular Filtration Rate) > 30 mL/min/1.73 m2

6. Healthy volunteers (cohort specific criteria): adults with no known pre-existing medical conditions.

Exclusion Criteria

1. Tachycardia (heart rate > 100, R-R interval < 600 ms)

2. NYHA IV

3. Previous coronary artery disease requiring intervention, including history of myocardial infarction including septal reduction therapies

4. Severely reduced renal function, defined as eGFR < 30 mL/min/1.73 m2

5. Severely reduced liver function (Child-Pugh class C), especially severe obstructive hepatobiliary disease

6. Phaeochromocytoma

7. Advanced cancer (with short/medium term prognosis)

8. History of chest radiation therapy

9. Diabetic patients

10. Severe valvular disease

11. Previous heart surgery

12. Left ventricular assist device (LVAD)

13. Severe pulmonary disease

14. Hypersensitivity to any medicinal products containing gadolinium

15. Hypersensitivity to the active substance of the IMP or to any of the excipients

16. Contraindications to MRI, including implanted cardiac devices/pacemakers

17. Participants not able to follow instructions necessary to conduct the MRI

18. Women of childbearing potential

19. Participation in other clinical studies with investigational drugs either concurrently or within the last 30 days

20. Previous participation in this clinical trial

21. History of ongoing drug abuse or alcoholism

22. Legal incapacity and/or other circumstances rendering the patient unable to understand the nature, scope, and possible impact of the trial

23. Investigator site staff and sponsor directly involved in the conduct of the study and their family members.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

IC TARGETS AS

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Oslo University Hospital, Department of Cardiology, Rikshospitalet Sognsvannsveien 20

Oslo, Oslo County, Norway

Countries

Norway

Other Identifiers

2023-508118-40-01

Identifier Type: CTIS

Identifier Source: secondary_id

MNC001

Identifier Type: -

Identifier Source: org_study_id