Evidence map›Paper›PMID 41410037›Full record

Trial reportCirculation2026

IMPROVE-DiCE, a 2-Part, Open-Label, Phase 2a Trial Evaluating the Safety and Effectiveness of Ninerafaxstat in Patients With Cardiometabolic Syndromes.

Moritz J Hundertmark, Sarah M Birkhoelzer, Clara Portwood, Adrienne G Siu, Violet Matthews, Andrew J Lewis, James Grist, Ferenc Mózes, John A Henry, Jai Patel and 15 more

Registry-linked trialAbstract readClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Circulation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04826159 (A Pharmacodynamic Study to Evaluate the Effects of IMB-1018972 on Myocardial Energetics, Metabolism, and Function in Patients With Type 2 Diabetes.), which is not on this map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04826159 phase2completednot on this map

A Pharmacodynamic Study to Evaluate the Effects of IMB-1018972 on Myocardial Energetics, Metabolism, and Function in Patients With Type 2 Diabetes.

TypeinterventionalSponsorImbria Pharmaceuticals, Inc.Ran2021 to 2024Enrolled49ConditionsType 2 Diabetes, Diabetic Cardiomyopathies, HFpEF - Heart Failure With Preserved Ejection FractionArmsIMB-1018972
3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Cardiac energetics in health and disease: a meta-analysis.European heart journal. Imaging methods and practice · 2026
    Article
  4. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors.

Moritz J Hundertmark *Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom (M.J.H., S.M.B., C.P., A.G.S., A.J.L., J.G., F.M., J.A.H., L.V., S.N., D.J.T., O.J.R.).
Sarah M Birkhoelzer *Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom (M.J.H., S.M.B., C.P., A.G.S., A.J.L., J.G., F.M., J.A.H., L.V., S.N., D.J.T., O.J.R.).
Clara PortwoodOxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom (M.J.H., S.M.B., C.P., A.G.S., A.J.L., J.G., F.M., J.A.H., L.V., S.N., D.J.T., O.J.R.).
Adrienne G SiuOxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom (M.J.H., S.M.B., C.P., A.G.S., A.J.L., J.G., F.M., J.A.H., L.V., S.N., D.J.T., O.J.R.).ORCID 0009-0008-5568-1145
Violet MatthewsOxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom (V.M., R.S.).ORCID 0000-0003-2146-5942
Andrew J LewisOxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom (M.J.H., S.M.B., C.P., A.G.S., A.J.L., J.G., F.M., J.A.H., L.V., S.N., D.J.T., O.J.R.).ORCID 0000-0002-3714-6711
James GristOxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom (M.J.H., S.M.B., C.P., A.G.S., A.J.L., J.G., F.M., J.A.H., L.V., S.N., D.J.T., O.J.R.).
Ferenc MózesOxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom (M.J.H., S.M.B., C.P., A.G.S., A.J.L., J.G., F.M., J.A.H., L.V., S.N., D.J.T., O.J.R.).
John A HenryOxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom (M.J.H., S.M.B., C.P., A.G.S., A.J.L., J.G., F.M., J.A.H., L.V., S.N., D.J.T., O.J.R.).ORCID 0000-0002-7650-0963
Jai PatelImbria Pharmaceuticals, Boston, MA (J.P., P.C., A.Y.).
Paul ChamberlinImbria Pharmaceuticals, Boston, MA (J.P., P.C., A.Y.).
Rizwan SarwarOxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom (V.M., R.S.).ORCID 0000-0003-3297-2528
Arash YavariImbria Pharmaceuticals, Boston, MA (J.P., P.C., A.Y.).
Hakim-Moulay DehbiComprehensive Clinical Trials Unit, University College London, London, United Kingdom (H.-M.D.).ORCID 0000-0002-0816-0178
Prashant RaoDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA (P.R., X.S., S.Z., J.M.R., R.E.G.).
Xu ShiDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA (P.R., X.S., S.Z., J.M.R., R.E.G.).ORCID 0000-0002-9473-0359
Shuning ZhengDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA (P.R., X.S., S.Z., J.M.R., R.E.G.).
Jeremy M RobbinsDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA (P.R., X.S., S.Z., J.M.R., R.E.G.).ORCID 0000-0002-9672-4841
Robert E GersztenDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA (P.R., X.S., S.Z., J.M.R., R.E.G.).ORCID 0000-0002-6767-7687
Michael P FrenneauxImperial College London (M.P.F.).ORCID 0000-0002-5055-8024
Ladislav ValkovičOxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom (M.J.H., S.M.B., C.P., A.G.S., A.J.L., J.G., F.M., J.A.H., L.V., S.N., D.J.T., O.J.R.).ORCID 0000-0003-2567-3642
Jack J J J MillerDepartment of Clinical Medicine, Aarhus University, Aarhus, Denmark (J.J.J.J.M.).ORCID 0000-0002-6258-1299
Stefan NeubauerOxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom (M.J.H., S.M.B., C.P., A.G.S., A.J.L., J.G., F.M., J.A.H., L.V., S.N., D.J.T., O.J.R.).ORCID 0000-0001-9017-5645
Damian J Tyler *Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom (M.J.H., S.M.B., C.P., A.G.S., A.J.L., J.G., F.M., J.A.H., L.V., S.N., D.J.T., O.J.R.).
Oliver J Rider *Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom (M.J.H., S.M.B., C.P., A.G.S., A.J.L., J.G., F.M., J.A.H., L.V., S.N., D.J.T., O.J.R.).ORCID 0000-0003-1295-7769

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundWe report IMPROVE-DiCE (Improve Diabetic Cardiac Energetics), a 2-part open-label, phase 2a trial evaluating the safety and effectiveness of ninerafaxstat, a novel therapeutic designed to enhance cardiac energetics. Between May and September 2021, part 1 enrolled patients with type 2 diabetes and obesity without heart failure with preserved ejection fraction (HFpEF). Between January 2023 and June 2024, part 2 enrolled patients with type 2 diabetes, obesity, and HFpEF.

methodsForty-two participants received 200 mg ninerafaxstat twice daily (part 1, n=21, 43% women, 72±0.5 years of age, 4-8 weeks; part 2, n=21, 29% women, 71±6 years of age, 12 weeks). Myocardial energetics (phosphocreatine-to-ATP ratio [PCr/ATP], primary outcome) and function (rest and dobutamine stress) were assessed before and after treatment using magnetic resonance imaging,

resultsIn part 1, in patients with diabetes and obesity but without HFpEF, the heart was characterized by impaired pyruvate dehydrogenase flux, reduced PCr/ATP, triglyceride deposition, and diastolic impairment. Treatment with ninerafaxstat was associated with improved PCr/ATP (+0.39±0.49 [95% CI, 0.16-0.62]; Cohen's

conclusionsThese mechanistic phase 2a study results show that ninerafaxstat is safely tolerated and improves myocardial energetics in participants with obesity and diabetes without or with clinically manifest HFpEF. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04826159.

Indexed as

Diabetes Mellitus, Type 2Energy MetabolismHeart FailureMetabolic SyndromeObesityAgedFemaleHumansMaleMiddle AgedStroke VolumeTreatment Outcomecardiac energy metabolismdiabetic cardiomyopathyHFpEFhyperpolarized MRmagnetic resonance imagingobesity

Identifiers

PMID41410037
PMCPMC12928817

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.