NCT04739215

Brief Summary

The main aim of this study is to identify the underlying mechanisms of Sodium-glucose co-transporter-2 (SGLT2) inhibitors which are associated to better outcomes in patients with Diabetes mellitus type 2 and Heart Failure with preserved Ejection Fraction.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
62

participants targeted

Target at P25-P50 for phase_4 diabetes-mellitus-type-2

Timeline
Completed

Started Jan 2021

Typical duration for phase_4 diabetes-mellitus-type-2

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 15, 2021

Completed
Same day until next milestone

Study Start

First participant enrolled

January 15, 2021

Completed
20 days until next milestone

First Posted

Study publicly available on registry

February 4, 2021

Completed
1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 30, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 30, 2022

Completed
Last Updated

February 4, 2021

Status Verified

February 1, 2021

Enrollment Period

2 years

First QC Date

January 15, 2021

Last Update Submit

February 1, 2021

Conditions

Diabetes Mellitus, Type 2Heart Failure With Preserved Ejection Fraction

Keywords

Diabetes mellitusHeart Failure

Outcome Measures

Primary Outcomes (2)

  • Functional Main Objective: Impact of iSGLT2 on LV diastolic properties in terms of the change in LV stiffness constant (S+) at the peak of exercise.

    Intrinsic diastolic properties will be analyzed by dynamic pressure-volume loop catheterization.

    Baseline vs 12 months

  • Main Structural Objective: Changes in serum levels of procollagen type I C-terminal propertied (PICP, ng/mL)

    We will measure the changes in serum levels of procollagen type I C-terminal propertied (PICP, ng/mL), a validated biomarker of collagen type I deposition

    Baseline vs 12 months

Secondary Outcomes (8)

  • Changes in LV stiffness constants (S+ and S-).

    Baseline vs 12 months

  • Changes in the slope, Emax, of the end-systolic pressure-volume relationship

    Baseline vs 12 months

  • Impact of iSGLT2 on myocardial remodeling.

    Baseline vs 12 months

  • Correlation of myocardial remodeling patterns with the intrinsic diastolic properties of chamber VI with systolic function.

    Baseline vs 12 months

  • Relative contribution of the intrinsic diastolic properties of the LV and the flow patterns on filling pressures and their modulation under treatment with iSGLT2.

    Baseline vs 12 months

  • +3 more secondary outcomes

Study Arms (3)

Clinical Trial: Experimental Arm

EXPERIMENTAL

Patients with heart failure with preserved ejection fraction and type 2 diabetes mellitus treated with Dapagliflozin (Forxiga) 10 mg, one capsule per day orally.

Drug: Dapagliflozin 10 MG [Farxiga]

Clinical Trial: Placebo Arm

PLACEBO COMPARATOR

Patients with heart failure with preserved ejection fraction and type 2 diabetes mellitus treated with Placebo in a similar pattern.

Drug: Placebo

Descriptive Study

NO INTERVENTION

Patients with heart failure with preserved ejection fraction but with no type 2 diabetes mellitus (n=10).

Interventions

Dapagliflozin 10 MG [Farxiga]DRUG

Dapagliflozin 10 mg / day oral

Clinical Trial: Experimental Arm
PlaceboDRUG

One Placebo capsule daily oral

Clinical Trial: Placebo Arm

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Diagnosis of DM2 based on the established criteria: HbA1c ≥ 6.5% (48 mmol / mol) and fasting plasma glucose ≥ 7.0 mmol / L (≥126 mg / dL) or 2-h after overload ≥ 11.1 mmol / L ( ≥ 200 mg / dL).
  • LVEF ≥ 50%.
  • Diagnosis of ICFEP according to clinical criteria, with a hospital admission in the previous 6 months with demonstration of diastolic dysfunction according to the echocardiographic criteria.
  • Stable clinical situation (\> 1 month after hospitalization due to IC decompensation).
  • Clinical indication of cardiac catheterization.
  • Signature of informed consent.

You may not qualify if:

  • Previous treatment with iSGLT2.
  • Significant coronary disease.
  • Aortic or mitral valve disease ≥ moderate (grades 3 or 4/4 for valve regurgitations)
  • Contraindications for dapagliflozin treatment according to the data sheet (hereditary galactose intolerance, Lapp lactase insufficiency or glucose-galactose malabsorption, moderate-severe renal failure -CrCl \<60 ml / min or eGFR \<60 ml / min / 1 , 73 m2-, severe hepatic insufficiency).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Hospital General Universitario Gregorio Maranon

Madrid, 280007, Spain

RECRUITING

Related Publications (4)

  • Kasner M, Westermann D, Lopez B, Gaub R, Escher F, Kuhl U, Schultheiss HP, Tschope C. Diastolic tissue Doppler indexes correlate with the degree of collagen expression and cross-linking in heart failure and normal ejection fraction. J Am Coll Cardiol. 2011 Feb 22;57(8):977-85. doi: 10.1016/j.jacc.2010.10.024.

    PMID: 21329845RESULT

  • Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, Mattheus M, Devins T, Johansen OE, Woerle HJ, Broedl UC, Inzucchi SE; EMPA-REG OUTCOME Investigators. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015 Nov 26;373(22):2117-28. doi: 10.1056/NEJMoa1504720. Epub 2015 Sep 17.

    PMID: 26378978RESULT

  • Perez Del Villar C, Savvatis K, Lopez B, Kasner M, Martinez-Legazpi P, Yotti R, Gonzalez A, Diez J, Fernandez-Aviles F, Tschope C, Bermejo J. Impact of acute hypertension transients on diastolic function in patients with heart failure with preserved ejection fraction. Cardiovasc Res. 2017 Jul 1;113(8):906-914. doi: 10.1093/cvr/cvx047.

    PMID: 28402411RESULT

  • Bermejo J, Yotti R, Perez del Villar C, del Alamo JC, Rodriguez-Perez D, Martinez-Legazpi P, Benito Y, Antoranz JC, Desco MM, Gonzalez-Mansilla A, Barrio A, Elizaga J, Fernandez-Aviles F. Diastolic chamber properties of the left ventricle assessed by global fitting of pressure-volume data: improving the gold standard of diastolic function. J Appl Physiol (1985). 2013 Aug 15;115(4):556-68. doi: 10.1152/japplphysiol.00363.2013. Epub 2013 Jun 6.

    PMID: 23743396RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 2Diabetes MellitusHeart Failure

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Glucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesHeart DiseasesCardiovascular Diseases

Study Officials

  • Javier Bermejo Thomas, MD, PhD

    Hospital General Universitario Gregorio Marañón

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Javier Bermejo Thomas, MD, PhD

CONTACT

(34) 91 5868279javier.bermejo@salud.madrid.org

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 15, 2021

First Posted

February 4, 2021

Study Start

January 15, 2021

Primary Completion

December 30, 2022

Study Completion

December 30, 2022

Last Updated

February 4, 2021

Record last verified: 2021-02

Locations

ES(1)