Evaluation of GeranylGeranylAcetone in Heart Failure With Preserved Ejection Fraction

NCT ID: NCT05672134

Last Updated: 2025-04-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

43 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-04-26

Study Completion Date

2024-08-30

Brief Summary

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The goal of this double-blind randomized, placebo-controlled cross-over trial is to evaluate the effectiveness of GerenylGeranylAcetone (GGA) in patients with Heart Failure with a preserved ejection fraction.

The main questions it aims to answer are:

* What is the effect of GGA on diastolic function?
* What is the effect of GGA on endothelial function?

Main study tasks:

* Participants will be treated with either GGA or placebo for 13 weeks. After this they will have a break (wash-out) period for 6 weeks and then cross over to the other study arm.
* Cardiac function will be measured using echocardiogram in all participants
* Renal measurements and endothelial measurements will be performed on the participants.
* Participants will perform a 5 minute walking distance test for functional capacity.
* Participants will fill out questionnaires to score signs \& symptoms.

Researchers will compare the patients to themselves to see if the drug improves diastolic- and endothelial function.

Detailed Description

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Conditions

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Heart Failure With Preserved Ejection Fraction

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

crossover multi-centre, double-blind, randomized control trial.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Experimental arm

Patients will receive 13 weeks of experimental treatment, followed by a 7 week wash-out period, continuing with 13 weeks of placebo as per crossover design.

Group Type EXPERIMENTAL

Iohexol measurement

Intervention Type DIAGNOSTIC_TEST

Invasive renal hemodynamic measurement of mGFR through the administration of Iohexol.

Geranylgeranylacetone (GGA)

Intervention Type DRUG

13 weeks of treatment with GGA/placebo orally, followed by a wash-out period of 6 weeks, then reversal of the treatment arms.

Echocardiography

Intervention Type DIAGNOSTIC_TEST

The investigators will perform echocardiography to find changes in cardiac function.

6-minute walking distance test

Intervention Type DIAGNOSTIC_TEST

6 minute walking distance test to compare exercise tolerance in participants.

EndoPAT

Intervention Type DIAGNOSTIC_TEST

Use of EndoPAT to measure endothelial function.

Para-amino Hippuric Acid test

Intervention Type DIAGNOSTIC_TEST

PAH-measurement to measure ERPF.

Electrocardiogram

Intervention Type DIAGNOSTIC_TEST

12-lead Electrocardiogram

Placebo arm

Patients will receive 13 weeks of placebo treatment, followed by a 7 week wash-out period, continuing with 13 weeks of experimental treatment as per crossover design.

Group Type PLACEBO_COMPARATOR

Iohexol measurement

Intervention Type DIAGNOSTIC_TEST

Invasive renal hemodynamic measurement of mGFR through the administration of Iohexol.

Geranylgeranylacetone (GGA)

Intervention Type DRUG

13 weeks of treatment with GGA/placebo orally, followed by a wash-out period of 6 weeks, then reversal of the treatment arms.

Echocardiography

Intervention Type DIAGNOSTIC_TEST

The investigators will perform echocardiography to find changes in cardiac function.

6-minute walking distance test

Intervention Type DIAGNOSTIC_TEST

6 minute walking distance test to compare exercise tolerance in participants.

EndoPAT

Intervention Type DIAGNOSTIC_TEST

Use of EndoPAT to measure endothelial function.

Para-amino Hippuric Acid test

Intervention Type DIAGNOSTIC_TEST

PAH-measurement to measure ERPF.

Electrocardiogram

Intervention Type DIAGNOSTIC_TEST

12-lead Electrocardiogram

Interventions

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Iohexol measurement

Invasive renal hemodynamic measurement of mGFR through the administration of Iohexol.

Intervention Type DIAGNOSTIC_TEST

Geranylgeranylacetone (GGA)

13 weeks of treatment with GGA/placebo orally, followed by a wash-out period of 6 weeks, then reversal of the treatment arms.

Intervention Type DRUG

Echocardiography

The investigators will perform echocardiography to find changes in cardiac function.

Intervention Type DIAGNOSTIC_TEST

6-minute walking distance test

6 minute walking distance test to compare exercise tolerance in participants.

Intervention Type DIAGNOSTIC_TEST

EndoPAT

Use of EndoPAT to measure endothelial function.

Intervention Type DIAGNOSTIC_TEST

Para-amino Hippuric Acid test

PAH-measurement to measure ERPF.

Intervention Type DIAGNOSTIC_TEST

Electrocardiogram

12-lead Electrocardiogram

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

1. Age≥ 50 years
2. Patients with a diagnosis of symptomatic chronic heart failure (New York Heart Association class II or III) AND preserved systolic LV function (LV ejection fraction or LVEF ≥ 50%) documented within the last 6 months AND evidence of diastolic LV dysfunction with at least 1 out of the following 4 criteria:

* HFA-PEFF score ≥5
* H2FPEF score ≥6
* HFpEF according to the 2021 ESC HF Guidelines (NT-proBNP\>125 pg/ml AND either LV mass indexed or LVMI \>95 g/m2 for women and \>115 g/m2 for men OR left atrial volume indexed or LAVI \>34 ml/m2 OR mean e; septal/lateral \< 9 cm/s) OR E/e' \>13 OR TR velocity at rest \>2,8m/s.
* Pulmonary capillary wedge pressure (PCWP) \>15 mmHg and/or \>25 mmHg during exercise.

Exclusion Criteria

1. Current acute decompensated heart failure, requiring hospitalization or augmented therapy with intravenous diuretics, vasodilators, and/or inotropic drugs
2. Acute coronary syndrome, transient ischemic attack/cerebrovascular accident, major surgery within the previous 3 months
3. Hemoglobin \<9 g/dl at screening
4. LVEF \<40% measured at any time point in the history of the patient
5. History of mitral valve repair or replacement
6. Presence of significant valvular disease defined as mitral valve regurgitation defined as grade ≥ 3+ MR; tricuspid valve regurgitation defined as grade ≥ 2+ TR; aortic valve disease defined as ≥ 2+ AR or \> moderate AS
7. Acute myocarditis within 3 months prior to randomization
8. Infiltrative cardiomyopathy
9. Genetic cardiomyopathy
10. Severe pulmonary disease requiring home oxygen or chronic oral steroid therapy
11. Precapillary pulmonary hypertension
12. BMI \>40 kg/m2
13. Estimated glomerular filtration rate (GFR) \<20 ml/min or \>90 ml/min
14. History of solid organ transplantation including kidney transplantation
15. Atrial fibrillation or atrial flutter with resting ventricular rate \>110 bpm
16. Not able to undergo the complete study protocol
17. Doubt about compliance
18. Pre-menopausal women who are nursing, pregnant, or of child-bearing potential and not practicing an acceptable method of birth control
19. Chronic absorption problems
20. Proven allergy for lactose products or cow-milk.
21. Proven allergy for Iodide-containing contrast, Iohexol or PAH.
22. Any documented or suspected malignancy or history of malignancy within 1 year prior to screening, except appropriately treated basal cell carcinoma of the skin or in situ carcinoma of the cervix
23. Currently enrolled in another investigational device or drug trial
24. Estimated life expectancy \<1 year
Minimum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Amsterdam UMC, location VUmc

OTHER

Sponsor Role lead

Responsible Party

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M. Louis Handoko

MD, PhD, Principal investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Louis Handoko, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Amsterdam University Medical Center

Adriaan Voors, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Groningen

Loek van Heerebeek, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Onze Lieve Vrouwe Gasthuis, Amsterdam

Locations

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Amsterdam UMC, loc VUmc

Amsterdam, North Holland, Netherlands

Site Status

Countries

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Netherlands

Other Identifiers

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NL 80684

Identifier Type: -

Identifier Source: org_study_id

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