ASCs in Recently Diagnosed Non-ischemic Heart Failure (ARIISE)

March 27, 2026 updated by: Cell to Cure ApS

A Danish, Double-blind, Randomized Placebo-controlled Clinical Trial Evaluating Allogeneic Adipose Tissue Derived Mesenchymal Stromal Cell Therapy in Patients With Recently Diagnosed Non-ishemic Heart Failure With Reduced Ejection Fraction

The goal of this clinical trial is to investigate the efficacy and safety of intravenous infusions of allogeneic adipose tissue-derived mesechymal stromal cells in patients with recently diagnosed non-ischemic heart failure in restoring cardiac function compared to placebo. The primary outcome of this trial is the change in left ventricular ejection fraction 6 month after treatment compared to placebo. Participants will be given two treatments with one month apart of either allogeneic adipose tissue-derived mesechymal stromal cells or placebo.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

Non-ischemic heart failure (NIHF) is the leading reason for heart transplantation. The disease can be caused by several different factors, which include genetic disposition, inflammation, hypertension, alcohol consumption, and arrhythmia. Regardless of the aetiology, immune activation in myocardium leads to collagen deposition and decreases the function of heart. There are currently no treatment options, which reverse the inflammatory component in NIHF.

For the past decade, cell therapy has been tested as treatment option for ischemic and non-ischemic heart failure. Especially the mesenchymal stromal cell (MSC) has shown encouraging results for their potential to improve cardiac function in patients with non-ischemic heart failure along with its safety. The cardiac improvement may be related to the immunomodulation as MSC is known by its ability to modulate the immune system and has successfully been applied clinically as a novel active immunosuppressor.

We aim to conduct a clinical trial in which patients recently diagnosed with NIHF will be randomized to either treatment with two intravenous infusions of allogeneic MSCs obtained from adipose tissue (C2C_ASC110) or placebo (Cryostor® CS10) 4 weeks apart. The objective is to evaluate the safety and effect of MSCs on cardiac function.

The long-term perspective is that the information gathered from this study can lead to a new treatment option for this specific group of patients, who currently have no further treatment options and a poor prognosis.

Study Type

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Copenhagen, Denmark, 2100
        • Cardiology Stem Cell Centre, Department of Cardiology, The Heart Centre, Rigshospitalet, University of Copenhagen, Denmark

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients above 18 years of age
  • Written informed consent
  • Anticipated to be able to participate during the entire study period
  • Diagnosed with non-ischemic heart failure with initial LVEF ≤ 40% and then up-titrated to maximal tolerable heart failure medication within the last 12 months
  • Symptomatic heart failure (NYHA II-III)
  • LVEF ≤ 45 % documented by echocardiography, CT or MRI performed after up-titration of heart failure medication (documentation of reduced LVEF at least after 1 and 3 months if implantation of a device either an Implantable Cardioverter Defibrillator (ICD) or Cardiac Resynchronisation Therapy (CRT), respectively)
  • Plasma Pro-BNP > 300 pg/ml (> 35 pmol/L) in patients with sinus rhythm and plasma Pro-BNP > 422 pg/ml (> 49 pmol/L) in patients with atrial fibrillation.

Exclusion Criteria:

  • NYHA I or IV heart failure
  • Documented ischemic heart failure
  • On-going alcohol abuse
  • Implantation of CRT within 3 months or ICD within 1 month
  • Acute coronary syndrome with elevation of CKMB (Creatine Phosphatase-Myocardial Band) or troponins, stroke or transitory cerebral ischemia within six weeks of inclusion
  • Expected to undergo screening for heart transplantation during the study time
  • Listed for heart transplantation
  • Other cardiac revascularization treatments to be performed
  • Moderate to severe aortic stenosis (valve area < 1.1 cm2) or clinically significant mitral valve disease
  • Diminished functional capacity for other reasons such as: chronic obstructive pulmonary disease (COPD) with forced expiratory volume (FEV) < 1 L/min or body mass index > 35kg/m2
  • Clinically significant anaemia (haemoglobin < 6 mmol/L), leukopenia (leucocytes < 2 109/L), leucocytosis (leucocytes >14 109/L) or thrombocytopenia (thrombocytes < 50 109/L)
  • History with malignant disease within five years of inclusion or current suspected malignancy - except treated skin cancer other than melanoma
  • Patients with known hypersensitivity to DMSO and Dextran-40.
  • Pregnant women
  • Other experimental treatment within four weeks from baseline tests
  • Participation in another interventional trial

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Allogeneic adipose tissue-derived mesenchymal stromal cells (C2C_ASC110)
Intravenous infusion of allogeneic adipose tissue-derived mesenchymal stromal cells (C2C_ASC110) 1 month apart.
Drug: Allogeneic adipose tissue-derived mesenchymal stem cells
Two intravenous infusions of C2C_ASC110 1 month apart. The C2C_ASC110 product contains 110 million cells.
Other Names:
  • C2C_ASC110
Placebo Comparator: CryoStor® CS10
Intravenous infusion of CryoStor® CS10 1 month apart.
Other: Cryostor CS10
Two intravenous infusions of CryoStor CS10 1 month apart.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in left ventricular ejection fraction (I)
Time Frame: From enrollment to 6 months after the last infusion of C2C_ASC110 and placebo.
Change in left ventricular ejection fraction 6 months after last C2C_ASC110 infusion compared to the placebo group.
From enrollment to 6 months after the last infusion of C2C_ASC110 and placebo.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in left ventricular end systolic volume
Time Frame: From enrollment to 7 months and to 12 months.
Changes in left ventricular end systolic volume
From enrollment to 7 months and to 12 months.
Change in left ventricular ejection fraction (II)
Time Frame: From enrollment to 7 months and to 12 months.
Change in left ventricular ejection fraction.
From enrollment to 7 months and to 12 months.
Changes in left ventricular end diastolic volume
Time Frame: From enrollment to 7 months and to 12 months.
Changes in left ventricular end diastolic volume.
From enrollment to 7 months and to 12 months.
Change in NYHA classification
Time Frame: From enrollment to 12 months.
Change in New York Heart Association (NYHA) classification. A scale from 1 to 4 describing the extent of heart failure by patient-reported symptoms, with class 1 denoting no symptoms and no limitations in ordinary physical activity and class 4 denoting symptoms and severe limitations in ordinary physical activity.
From enrollment to 12 months.
Change in KCCQ questionnaire score
Time Frame: From enrollment to 12 months.
Change in Kansas City Cardiomyopathy (KCCQ) questionnaire score. A scale from 0 to 100 describing health status in patients with heart failure, with 0 denoting the worst possible health status and 100 denotes the best possible health status.
From enrollment to 12 months.
Change in EQ5D5L questionnaire score
Time Frame: From enrollment to 12 months.
Change in European Quality of Life - 5 Dimensions (EQ5D5L) questionnaire score. A scale from 0 to 100 describing health related quality of life, with 0 denoting the worst possible quality of life and 100 denoting the best possible quality of life.
From enrollment to 12 months.
Change in 6 minutes walking test
Time Frame: From enrollment to 12 months.
Change in 6 minutes walking test.
From enrollment to 12 months.
Change in Pro-BNP
Time Frame: From enrollment to 12 months.
Change in Pro-BNP.
From enrollment to 12 months.
Incidence and severity of adverse reactions
Time Frame: From the first infusion of C2C_ASC110 and placebo to 12 months.
Incidence and severity of serious adverse reactions and suspected unexpected serious adverse reactions.
From the first infusion of C2C_ASC110 and placebo to 12 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cell to Cure ApS

Investigators

  • Principal Investigator: Abbas A Qayyum, MD MSc PhD, Cardiology Stem Cell Centre, Department of Cardiology, The Heart Centre, Rigshospitalet, Copenhagen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

March 1, 2026

Primary Completion (Estimated)

September 1, 2028

Study Completion (Estimated)

September 1, 2028

Study Registration Dates

First Submitted

February 3, 2025

First Submitted That Met QC Criteria

February 19, 2025

First Posted (Actual)

February 21, 2025

Study Record Updates

Last Update Posted (Actual)

April 1, 2026

Last Update Submitted That Met QC Criteria

March 27, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ARIISE
  • 2025-520837-22-00 (Ctis)
  • U1111-1315-7011 (Other Identifier: WHO universal trial number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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