Investigation of cardiac metabolism in patients with heart failure using hyperpolarized MRI

2024-515414-40-00 Phase I and Phase II (Integrated) - Other Ongoing, recruiting

Start 1 Dec 2019 · Status Ongoing, recruiting · 1 EU/EEA countries · 1 sites

Overview

Sponsor-declared trial summary

Phase Phase I and Phase II (Integrated) - Other
Status Ongoing, recruiting
Participants planned 30
Countries 1
Sites 1

Heart failure

To visualize and quantify pyruvate metabolism of the heart in patients with heart disease and correlate it to current clinical diagnostic scanning modalities.

Key facts

Sponsor
Region Midtjylland
Participant type
Patients, Healthy volunteers
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Cardiovascular Diseases [C14], Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01]
Trial duration
1 Dec 2019 → ongoing
Decision date (initial)
2024-09-16
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
No

External identifiers

EU CT number
2024-515414-40-00
EudraCT number
2018-003533-15

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Diagnosis

To visualize and quantify pyruvate metabolism of the heart in patients with heart disease and correlate it to current clinical diagnostic scanning modalities.

Conditions and MedDRA coding

Heart failure

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

  1. Chronic heart failure (Heart failure with both reduced and preserved EF are allowed) > 18 years of age. Left ventricular Ejection Fraction (LVEF) of 10 – 60 % Adequate hematologic and organ function, i.e. ANC at least 1.500/uL Platelet count >100/uL Se creatinine up to 1.5 x UNL or creatinine clearance at least 30 ml/min Women who are not postmenopausal or surgically sterile must have a negative serum or urine pregnancy test performed at time of inclusion in the study. Safe and highly effective contraception must be used throughout the study meaning either hormonal anti-conception or an anti-fertility intrauterine device. If the partner is non fertile or the patient has no sexual activities, this is also accepted. Non-insulin dependent Diabetes mellitus is allowed Danish speaking Able and willing to comply after informed consent For substudy 1A only: Ischemic heart disease and referral to viability testing at the Department of Clinical Physiology and Nuclear Medicine at Aarhus University Hospital, Skejby.

Exclusion criteria 1

  1. Not able or willing to receive heart failure therapy Patients not willing to participate Uncontrolled serious medical condition, such as uncontrolled heart disease, uncontrolled diabetes, intestinal obstruction, uncontrolled hypertension, or recent cerebral ischemia Receiving more than 50% of taget dose of ACE-inhibitor and betablockers before inclusion in study 1 (this does not apply for substudy 1A) Estimated Glomerular Filtration Rate (eGFR) <30 mL/min Insulin dependent Diabetes Mellitus Intolerance to Pyruvate

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Metabolic in vivo flux through the PDC in the myocardium in humans. Co-primary endpoints are: a) [13C]-bicarbonate/[1-13C]-pyruvate ratio, b) [1-13C]-lactate / [1-13C]-pyruvate ratio and [1-13C]-lactate / [1-13C]-bicarbonate ratio. The latter gives ratio indices of PDC-mediated pyruvate oxidation and lactate production via lactate dehydrogenase.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Hyperpolarized [1-13C]pyruvate

PRD10284730 · Product

Active substance
Pyruvic Acid
Pharmaceutical form
INJECTION
Route of administration
IV INJECTION, IV INFUSION
Authorisation status
Not Authorised
MA holder
AARHUS UNIVERSITY
Paediatric formulation
No
Orphan designation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Midtjylland

Sponsor organisation
Region Midtjylland
Address
Palle Juul-Jensens Boulevard 99
City
Aarhus N
Postcode
8200
Country
Denmark

Scientific contact point

Organisation
Region Midtjylland
Contact name
Henrik Wiggers

Public contact point

Organisation
Region Midtjylland
Contact name
Henrik Wiggers

Third parties 1

OrganisationCity, countryDuties
Aarhus Universitet
ORG-100028380
Aarhus N, Denmark On site monitoring

Locations

1 EU/EEA country · 1 investigational sites

By country

CountryMS statusPlanned subjectsSites
Denmark Ongoing, recruiting 30 1
Rest of world 0

Investigational sites

Denmark

1 site · Ongoing, recruiting
Aarhus Universitetshospital
Cardiology, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
Denmark 2019-12-01 2019-12-06

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) Protocol 6
Recruitment arrangements (for publication) Recruitment arrangements 1
Subject information and informed consent form (for publication) Deltagerinformation Pilotstudie raske 1
Subject information and informed consent form (for publication) Deltagerinformation Studie 1 og 2 1
Subject information and informed consent form (for publication) Deltagerinformation substudie 1A 1
Subject information and informed consent form (for publication) Samtykkeerklring 1
Summary of Product Characteristics (SmPC) (for publication) Pyruvic acid 1

Application history

3 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-08-30 Denmark Acceptable
2024-09-16
2024-09-16
2 NON SUBSTANTIAL MODIFICATION NSM-1 2025-04-28 Denmark Acceptable
2024-09-16
2025-04-28
3 NON SUBSTANTIAL MODIFICATION NSM-2 2026-02-13 Denmark Acceptable
2024-09-16
2026-02-13