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Diabetic CardiomyopathiesPhase 3NCT04083339

Safety and Efficacy of AT-001 in Patients With Diabetic Cardiomyopathy

A Phase 3 study testing AT-001 in people with Diabetic Cardiomyopathies, run by Applied Therapeutics, Inc. at 79 sites in 10 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This is a multicenter, randomized, placebo-controlled, 2-part study to evaluate the safety and efficacy of AT-001 in adult patients (N=675) with Diabetic Cardiomyopathy at high risk of progression to overt heart failure. Read more about this study

Who is it for?
Ages 40 years and older
Conditions the study is for
Diabetic Cardiomyopathies
What is being tested?
AT-001
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
675 participants
Where
79 sitesin 10 countries
Study dates
20 Sep 2019to Dec 2025
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 40 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Type 2 Diabetes Mellitus
  • Diabetic cardiomyopathy
  • Peak VO2 < 75% of predicted normal value based on age and gender

Who cannot join

  • Prior diagnosis or signs/symptoms of overt/symptomatic heart failure / stage C heart failure
  • Prior echocardiogrphic measurement of ejection fraction (EF) < 40%
  • Prior acute coronary syndrome (ACS), coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI), coronary artery disease (CAD) or stroke
  • Severe or moderate cardiac valve disease requiring intervention
  • Clinically significant arrhythmia
  • Prior diagnosis of congenital, infective, toxic, infiltrative, post-partum, or hypertrophic cardiomyopathy
Show all 9Show fewer
  • Blood pressure > 140 mmHg (systolic) or > 90 mmHg (diastolic) at screening
  • HbA1c >8.5% at screening
  • Severe disease that would impact the performance of a cardio-pulmonary exercise test

Trial locations and contacts

79 sites in 10 countries.

79 sites in 10 countries

United States28 sites

  • Westside Medical Associates of Los Angeles

    Beverly Hills, California, 90211

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • Remington Davis, Inc.

    Columbus, Ohio, 43215

  • ALL Medical Research, LLC

    Cooper City, Florida, 33024

  • Dallas Diabetes Research Center

    Dallas, Texas, 75230

  • Southwest Family Medicine Associates

    Dallas, Texas, 75235

  • University of Texas Southwestern

    Dallas, Texas, 75390

  • Mountain View Clinical Research - Greer

    Greer, South Carolina, 29651

  • Mountain View Clinical Research

    Greer, South Carolina, 29651

  • New Generation of Medical Research

    Hialeah, Florida, 33016

  • Juno Research, LLC - Northwest Site

    Houston, Texas, 77040

  • Juno Research, LLC - Southwest Houston Site

    Houston, Texas, 77074

  • Universty of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • Holston Medical Group

    Kingsport, Tennessee, 37660

  • University of California, San Diego (UCSD)

    La Jolla, California, 92093

  • FMC Science

    Lampasas, Texas, 76550

  • Clinical Trials Research

    Lincoln, California, 95648

  • South Oklahoma Heart Research

    Oklahoma City, Oklahoma, 73135

  • University of California - Irvine Medical Center

    Orange, California, 92868

  • Broward Research Center

    Pembroke Pines, Florida, 33024

  • UnityPoint Health - Methodist Hospital

    Peoria, Illinois, 61602

  • Progressive Medical Research

    Port Orange, Florida, 32127

  • St. Louis Heart and Vascular Cardiology

    St Louis, Missouri, 63136

  • Metabolic Institute of America

    Tarzana, California, 91356

  • Chear Center LLC

    The Bronx, New York, 10455

  • Montefiore Medical Center

    The Bronx, New York, 10467

  • Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center

    Torrance, California, 90509

Other trials in United States

Canada9 sites

  • LMC Diabetes & Endocrinology Ltd. - Brampton

    Brampton, Ontario, L6S 0C6

  • C-Endo - Endocrinology Centre

    Calgary, Alberta, T2V 4J2

  • Ecogene-21

    Chicoutimi, Quebec, G7H 7K9

  • LMC Diabetes & Endocrinology Ltd. - Thornhill

    Concord, Ontario, L4K 4M2

  • LMC Diabetes & Endocrinology Ltd. - Etobicoke

    Etobicoke, Ontario, M9R 4E1

  • Centre for Studies in Family Medicine, Western Centre for Public Health and Family Medicine, Western University

    London, Ontario, N6G 2M1

  • Institut Universitaire de Cardiologie et de Pneumologie De Quebec

    Québec, Quebec, G1V 4G5

  • LMC Diabetes & Endocrinology Ltd. - Toronto

    Toronto, Ontario, M4G 3E8

  • BC Diabetes

    Vancouver, British Columbia, V5Y 3W2

Other trials in Canada

Poland9 sites

  • NZOZ Specjalistyczny Osrodek Internistyczno - Diabetologiczny

    Bialystok, 15-435

  • Topolowa MEDICENTER Mrózek & wspólnicy sp.j.

    Krakow, 31-506

  • Centrum Twojego Zdrowia

    Krakow, 31-526

  • ETG Lodz

    Lodz, 90-302

  • Praktyka Lekarska Ewa Krzyzagorska

    Poznan, 61-655

  • Prywatny Gabinet Lekarski Centrum Medyczne Diabetika

    Radom, 26-600

  • Centrum Medyczne Medyk Stanislaw Mazur Sp. z o.o. SK

    Rzeszów, 35-005

  • Centrum Chorob Serca w USK

    Wroclaw, Borowska, 50-556

  • 4 Wojskowy Szpital Kliniczny z Poliklinika Samodzielny Publiczny ZOZ we Wroclawiu

    Wroclaw, 50-981

Other trials in Poland

Australia7 sites

  • Prince Charles Hospital

    Chermside, Queensland, 4032

  • Barwon Health-University Hospital Geelong

    Geelong, Victoria, 3220

  • Austin Health

    Heidelberg, Victoria, 3084

  • University of Tasmania at Hobart

    Hobart, Tasmania, 7001

  • Baker Heart and Diabetes Institute

    Melbourne, Victoria, 3004

  • CORE Research Group Pty. Ltd.

    Milton, Queensland, 4064

  • AusTrials

    Taringa, Queensland, 4068

Other trials in Australia

Spain7 sites

  • Hospital Abente y Lago (Complejo Universitario de la Coruña)

    A Coruña, 15001

  • Hospital Germans Trias i Pujol

    Badalona, Barcelona, 08916

  • Hospital de la Santa Creu i Sant Pau Barcelona

    Barcelona, 08041

  • Hospital Universitario Reina Sofia

    Córdoba, 14004

  • Hospital Clinico Universitario Virgen de la Arrixaca

    El Palmar, Murcia, 30120

  • Hospital Universitario Virgen Macarena

    Seville, 41009

  • Hospital Clinico Universitario de Valencia

    Valencia, 46010

Other trials in Spain

Germany5 sites

  • Herz-und Diabeteszentrum NRW Universitaetsklinik der Ruhr-Universitaet Bochum

    Bad Oeynhausen, North Rhine-Westphalia, 32545

  • Klinische Forschung Berlin GbR

    Berlin, 10787

  • Cardiologicum Pirna und Dresden

    Dresden, Saxony, 01277

  • ZKS - Zentrum Klinische Studien Sudbrandenburg GmbH

    Elsterwerda, 04910

  • Klinikum Frankfurt (Oder) GmbH

    Frankfurt (Oder), Brandenburg, 15236

Other trials in Germany

United Kingdom5 sites

  • Ninewells Hospital & Medical School

    Dundee, DD1 9SY

  • CPS Research

    Glasgow, G20 0XA

  • Glenfield hospital

    Leicester, LE3 9QP

  • Barts and The London School of Medicine & Dentistry

    London, EC1M 6BQ

  • Wythenshawe Hospital

    Manchester, M23 9Lt

Other trials in United Kingdom

France4 sites

  • Hôpital Jean-Verdier - AP-HP; Service Endocrinologie Diabétologie Nutrition

    Bondy, 93140

  • CHU Henri Mondor

    Créteil, 94000

  • CHU de Nantes, Clinique d'Endocrinologie

    Nantes, 44093

  • Centre Hospitalier de Valenciennes

    Valenciennes, 59322

Other trials in France

Czechia3 sites

  • Edumed s.r.o.

    Jaroměř, 55101

  • Nemocnice Pardubickeho kraje, a.s., Nemocnice Pardubice

    Pardubice, 532 03

  • Vseobecna fakultni nemocnice v Praze

    Prague, 128 08

Other trials in Czechia

Hong Kong2 sites

  • Erik Yee Mun George Fung

    Shatin

  • Prince of Wales Hospital; Chinese University of Hong Kong; Dept of Medicine and Therapeutics

    Shatin

Other trials in Hong Kong

About this study

Official title: Aldose Reductase Inhibition for Stabilization of Exercise Capacity in Heart Failure (ARISE-HF): A Multicenter, Randomized, Placebo-Controlled Study to Evaluate the Safety and Efficacy of AT-001 in Patients With Diabetic Cardiomyopathy

This is a multicenter, randomized, placebo-controlled, 2-part study to evaluate the safety and efficacy of AT-001 in adult patients (N=675) with Diabetic Cardiomyopathy at high risk of progression to overt heart failure.

Read the detailed description

The study consists of two consecutive parts: Part A and Part B. Part A will evaluate the safety and efficacy of two doses of AT-001 vs placebo. The primary objective of Part A is to demonstrate that AT-001 improves or prevents the decline of functional capacity in patients with Diabetic Cardiomyopathy. Part B is an extension of at least 12 months that will evaluate the safety and efficacy of chronic administration of AT-001 vs placebo in the same patients who had previously been evaluated in Part A. Assessments in Part B will include safety endpoints and exploratory clinical efficacy endpoints, i.e. death and hospitalization due to a cardiac event.

Being tested
AT-001, Placebo
Keywords
Type 2 Diabetes, Aldose Reductase Inhibitor, Stage B Heart Failure, Stage C Heart Failure, Cardiopulmonary Exercise Test
Medical subject headings
Diabetic Cardiomyopathies, Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AT-001Drug

    AT-001 will be administered as 3 capsules twice daily, before breakfast and before dinner.

    At present AT001 is the sole name for the active substance. No INN/genetic name is available to date

  • PlaceboDrug

    Matching placebo will be administered as 3 capsules twice daily, before breakfast and before dinner

Study groups in NCT04083339
Study groupRoleWhat they receive
AT-001 High doseExperimentalThe total daily doses will be of 3g. The dose selection and the frequency of dosing was based on the results of the phase 1/2 study demonstrating that 3g/day of AT-001 is capable of producing the maximum inhibition of the production of sorbitol (a pharmacodynamic biomarker of biological activity).
Receives: Drug: AT-001
AT-001 Low DoseExperimentalThe total daily doses will be of 2g. The dose selection and the frequency of dosing was based on the results of the phase 1/2 study demonstrating that 2g/day of AT-001 is capable of producing a sufficient inhibition of the production of sorbitol (a pharmacodynamic biomarker of biological activity).
Receives: Drug: AT-001
Placebo ComparatorPlacebo comparatorPlacebo capsules will be used as comparator
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Peak VO2 during cardio-pulmonary exercise test (CPET);

    Changes in Peak VO2 during cardio-pulmonary exercise test (CPET) from baseline to approximately Month 15 (15-18 months). A CPET may be repeated at approximately Month 27 (27-30 months).

    Measured: 15 months after randomization]

Secondary outcomes (3)

  1. Progression to overt heart failure (Stage C Heart Failure)

    Defined by the occurrence of one of the following events: cardiovascular death, hospitalization for heart failure, urgent heart failure visit, new diagnosis of heart failure

    Measured: 27 months after randomization

  2. Changes in NT-proBNP

    Changes in NT-proBNP may reflect worsening of cardiomyopathy over time

    Measured: 27 months after randomization

  3. Changes in the modified Kansas City Cardiomyopathy Questionnaire (KCCQ) score

    Changes in the modified KCCQ may reflect deterioration of clinical status over time

    Measured: 27 months after randomization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Sep 2019
  2. Study start20 Sep 2019
  3. Primary completionDec 2023 (estimated)
  4. Study completionDec 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
675 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04083339
Sponsor's protocol ID
AT-001-2001
Status last verified
Dec 2022
First submitted
23 Aug 2019
Last updated
8 Dec 2022
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Batista JL, Liu Y, Butler J, Del Prato S, Ezekowitz JA, Lam CSP, Marwick TH, Rosenstock J, Tang WHW, Perfetti R, Urbinati A, Zannad F, Ilonze O, Januzzi JL. Racial outcomes in patients with diabetic cardiomyopathy treated with an aldose reductase inhibitor: the ARISE-HF trial. Open Heart. 2026 Jul 31;13(2):e004312. doi: 10.1136/openhrt-2026-004312.

    PubMed 42538062

  • Blumer V, Januzzi JL Jr, Liu Y, Butler J, Ezekowitz JA, Perfetti R, Rosenstock J, Del Prato S, Tang WHW, Urbinati A, Zannad F, Lewis GD, Solomon SD, Hedge S, Ibrahim NE, Lam CSP. Sex Differences in Diabetic Cardiomyopathy and Treatment Response to AT-001: Insights From the ARISE-HF Study. JACC Heart Fail. 2026 Jan;14(1):102433. doi: 10.1016/j.jchf.2025.02.015. Epub 2025 May 8.

    PubMed 40338768

  • Siddiqi TJ, Liu Y, Zannad F, Tang WHW, Solomon S, Rosenstock J, Perfetti R, Marwick TH, Lewis GD, Lam CSP, Ibrahim NE, Ezekowitz J, Del Prato S, Butler J, Januzzi JL. Health status in stage B heart failure from diabetic cardiomyopathy baseline results from ARISE-HF. J Diabetes Complications. 2025 Jul;39(7):109059. doi: 10.1016/j.jdiacomp.2025.109059. Epub 2025 Apr 25.

    PubMed 40315802

  • Tang WHW, Liu Y, Butler J, Del Prato S, Ezekowitz JA, Ibrahim NE, Lam CSP, Marwick TH, Perfetti R, Rosenstock J, Solomon SD, Zannad F, Januzzi JL, Lewis GD. Impaired Exercise Capacity in High-Risk Diabetic Cardiomyopathy: The ARISE-HF Cardiopulmonary Exercise Testing Subanalysis. Circ Heart Fail. 2025 Mar;18(3):e012200. doi: 10.1161/CIRCHEARTFAILURE.124.012200. Epub 2025 Jan 30.

    PubMed 39882614

  • Marwick TH, Lam C, Liu Y, Del Prato S, Rosenstock J, Butler J, Ezekowitz J, Ibrahim NE, Tang WHW, Zannad F, Perfetti R, Januzzi JL. Echocardiographic phenotypes of diabetic myocardial disorder: evolution over 15 months follow-up in the ARISE-HF trial. Cardiovasc Diabetol. 2025 Jan 13;24(1):16. doi: 10.1186/s12933-024-02554-y.

    PubMed 39806375

  • Gouda P, Liu Y, Butler J, Del Prato S, Ibrahim NE, Lam CSP, Marwick T, Rosenstock J, Tang W, Zannad F, Januzzi J, Ezekowitz J. Relationship between NT-proBNP, echocardiographic abnormalities and functional status in patients with subclinical siabetic cardiomyopathy. Cardiovasc Diabetol. 2024 Aug 2;23(1):281. doi: 10.1186/s12933-024-02378-w.

    PubMed 39095808

  • Batista JL, Liu Y, Butler J, Del Prato S, Ezekowitz JA, Lam CSP, Marwick TH, Rosenstock J, Tang WHW, Perfetti R, Urbinati A, Zannad F, Januzzi JL Jr, Ibrahim NE. Racial Differences in Diabetic Cardiomyopathy: The ARISE-HF Trial. J Am Coll Cardiol. 2024 Jul 16;84(3):233-243. doi: 10.1016/j.jacc.2024.04.053.

    PubMed 38986667

  • Januzzi JL Jr, Butler J, Del Prato S, Ezekowitz JA, Ibrahim NE, Lam CSP, Lewis GD, Marwick TH, Perfetti R, Rosenstock J, Solomon SD, Tang WHW, Zannad F. Randomized Trial of a Selective Aldose Reductase Inhibitor in Patients With Diabetic Cardiomyopathy. J Am Coll Cardiol. 2024 Jul 9;84(2):137-148. doi: 10.1016/j.jacc.2024.03.380. Epub 2024 Apr 8.

    PubMed 38597864

  • Januzzi JL, Del Prato S, Rosenstock J, Butler J, Ezekowitz J, Ibrahim NE, Lam CSP, Marwick T, Wilson Tang WH, Liu Y, Mohebi R, Urbinati A, Zannad F, Perfetti R. Characterizing diabetic cardiomyopathy: baseline results from the ARISE-HF trial. Cardiovasc Diabetol. 2024 Feb 1;23(1):49. doi: 10.1186/s12933-024-02135-z.

    PubMed 38302936

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing AT-001 in people with Diabetic Cardiomyopathies, run by Applied Therapeutics, Inc. at 79 sites in 10 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 8 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 79 sites in United States, Canada, Poland, Australia, Spain and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Peak VO2 during cardio-pulmonary exercise test (CPET); (time frame: 15 months after randomization]). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04083339, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Dec 2022.

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