Heart Failure With Preserved Ejection FractionPhase 2GLADIATORNCT05672134
Evaluation of GeranylGeranylAcetone in Heart Failure With Preserved Ejection Fraction
A Phase 2 study testing Iohexol measurement, Geranylgeranylacetone (GGA) and Echocardiography in people with Heart Failure With Preserved Ejection Fraction, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Heart Failure With Preserved Ejection Fraction
- What is being tested?
- Iohexol measurement, Geranylgeranylacetone (GGA) and Echocardiography
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 43 participants
- Where
- 1 siteNetherlands
- Study dates
- 26 Apr 2023to 30 Aug 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age≥ 50 years
- 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.
Who cannot join
- Current acute decompensated heart failure, requiring hospitalization or augmented therapy with intravenous diuretics, vasodilators, and/or inotropic drugs
- Acute coronary syndrome, transient ischemic attack/cerebrovascular accident, major surgery within the previous 3 months
- Hemoglobin <9 g/dl at screening
- LVEF <40% measured at any time point in the history of the patient
- History of mitral valve repair or replacement
- 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
Show all 24Show fewer
- Acute myocarditis within 3 months prior to randomization
- Infiltrative cardiomyopathy
- Genetic cardiomyopathy
- Severe pulmonary disease requiring home oxygen or chronic oral steroid therapy
- Precapillary pulmonary hypertension
- BMI >40 kg/m2
- Estimated glomerular filtration rate (GFR) <20 ml/min or >90 ml/min
- History of solid organ transplantation including kidney transplantation
- Atrial fibrillation or atrial flutter with resting ventricular rate >110 bpm
- Not able to undergo the complete study protocol
- Doubt about compliance
- Pre-menopausal women who are nursing, pregnant, or of child-bearing potential and not practicing an acceptable method of birth control
- Chronic absorption problems
- Proven allergy for lactose products or cow-milk.
- Proven allergy for Iodide-containing contrast, Iohexol or PAH.
- 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
- Currently enrolled in another investigational device or drug trial
- Estimated life expectancy <1 year
Trial locations and contacts
1 site in 1 country.
About this study
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:
Read more
- 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.
- Being tested
- Iohexol measurement, Geranylgeranylacetone (GGA), Echocardiography, 6-minute walking distance test, EndoPAT
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Iohexol measurementDiagnostic test
Invasive renal hemodynamic measurement of mGFR through the administration of Iohexol.
Geranylgeranylacetone (GGA)Drug
13 weeks of treatment with GGA/placebo orally, followed by a wash-out period of 6 weeks, then reversal of the treatment arms.
EchocardiographyDiagnostic test
The investigators will perform echocardiography to find changes in cardiac function.
6-minute walking distance testDiagnostic test
6 minute walking distance test to compare exercise tolerance in participants.
EndoPATDiagnostic test
Use of EndoPAT to measure endothelial function.
Para-amino Hippuric Acid testDiagnostic test
PAH-measurement to measure ERPF.
ElectrocardiogramDiagnostic test
12-lead Electrocardiogram
| Study group | Role | What they receive |
|---|---|---|
| Experimental arm | Experimental | 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. Receives: Diagnostic Test: Iohexol measurement; Drug: Geranylgeranylacetone (GGA); Diagnostic Test: Echocardiography; Diagnostic Test: 6-minute walking distance test; Diagnostic Test: EndoPAT; Diagnostic Test: Para-amino Hippuric Acid test; Diagnostic Test: Electrocardiogram |
| Placebo arm | Placebo comparator | 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. Receives: Diagnostic Test: Iohexol measurement; Drug: Geranylgeranylacetone (GGA); Diagnostic Test: Echocardiography; Diagnostic Test: 6-minute walking distance test; Diagnostic Test: EndoPAT; Diagnostic Test: Para-amino Hippuric Acid test; Diagnostic Test: Electrocardiogram |
What is being measured
The primary outcome is the main question the study is designed to answer.
Filling pressures
Changes in echocardiography determined filling pressures (E/e')?
Measured: after 13 weeks of treatment
Endothelial function
Changes in EndoPAT®-derived reactive hyperemia index (RHI)
Measured: after 13 weeks of treatment
Secondary outcomes (22)
Left atrial volumes
Changes in echogardiographic measured left atrial volume index (LAVI)
Measured: After 13 weeks of treatment
Left atrial global strain
Changes in echogardiographic measured LA global strain (LAGS)
Measured: After 13 weeks of treatment
Left atrial emptying fractions
Changes in echogardiographic LA emptying fractions. Formula: (LA maximum volume-LA minimum volume)/LA maximum volume × 100%
Measured: After 13 weeks of treatment.
Left Ventricular global longitudinal strain
Changes in echocardiographically determinded LV global longitudinal strain (LGS)
Measured: Ater 13 weeks of treatment
Left Ventricular Myocardial relaxation
Change in echocardiographically determined myocardial relaxation (e')
Measured: Ater 13 weeks of treatment
Left Ventricular distensibility
Change in echocardiographically determined LV distensibility, measured by E.
Measured: After 13 weeks of treatment
Right Ventricular systolic function
Change in echocardiographically determined RV TAPSE
Measured: After 13 weeks of treatment
Pulmonary Artery Pressure
Change in echocardiographically determined PAP
Measured: After 13 weeks of treatment
Patient reported symptoms
Evaluation of symptoms using New York Heart Association class (NYHA)
Measured: After 13 weeks of treatment
Quality of life assessment
Evaluation of quality of life using the Kansas City Cariomyopathy Questionnaire
Measured: After 13 weeks of treatment.
Functional capacity
Evaluation of Functional Capacity using 6-minute walking distance test (6MWD)
Measured: After 13 weeks of treatment.
CRP (inflammatory biomarker)
Changes in CRP concentration in serum
Measured: After 13 weeks of treatment
Nitrosated hemoglobin (microvascular marker)
Changes in Nitrosated hemoglobin (Hb(NO)4) concentration in serum
Measured: After 13 weeks of treatment
Nitrate (microvascular marker)
Changes in nitrate concentration in serum
Measured: After 13 weeks of treatment
Endothelin-1 (microvascular marker)
Changes in Endothelin-1 concentration in serum
Measured: After 13 weeks of treatment
H2S (microvascular marker)
Changes in H2S concentration in serum
Measured: After 13 weeks of treatment
Measured Glomerular Filtration Rate (mGFR)
Changes in mGFR using Iohexol measurements in urine
Measured: After 13 weeks of treatment
Effective Renal Plasma Flow (ERPF)
Changes in ERPF using PAH-measurements in urine
Measured: After 13 weeks of treatment
Renal vascular resistance (RVR)
Changes in intrakidney hemodynamic function (Systemic Blood pressure / Renal Blood Flow)
Measured: After 13 weeks of treatment
Urine Albumine Creatinin Ratio
Changes in UACR concentration measured in urine.
Measured: After 13 weeks of treatment
Neutrophil gelatinase associated lipocalin (NGAL)
Changes in NGAL concentration measured in urine and serum
Measured: After 13 weeks of treatment
Kidney Injury marker 1 (KIM-1)
Changes in KIM-1 concentration measured in urine and serum
Measured: After 13 weeks of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jan 2023
- Study start26 Apr 2023
- Primary completion30 Aug 2024
- Study completion30 Aug 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart Failure With Preserved Ejection FractionStudies of the same condition, open and under way.
- More trials run by Amsterdam UMC, location VUmcThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- crossover multi-centre, double-blind, randomized control trial.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amsterdam UMC, location VUmc
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, M. Louis Handoko, VU University of Amsterdam
- Investigators
- Louis Handoko, MD, PhD, Principal investigator, Amsterdam University Medical CenterAdriaan Voors, MD, PhD, Principal investigator, University Medical Center GroningenLoek van Heerebeek, MD, PhD, Principal investigator, Onze Lieve Vrouwe Gasthuis, Amsterdam
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05672134
- Sponsor's protocol ID
- NL 80684
- Acronym
- GLADIATOR
- Status last verified
- Apr 2023
- First submitted
- 8 Jun 2022
- Last updated
- 1 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of GeranylGeranylAcetone in Heart Failure With Preserved Ejection Fraction
- ClinicalTrials.gov ID
- NCT05672134
- Acronym / sponsor ID
- GLADIATOR / NL 80684
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- Amsterdam UMC, location VUmcUniversity, hospital or other
- Study start
- 26 Apr 2023 (actual)
- Primary completion
- 30 Aug 2024 (actual)
- Study completion
- 30 Aug 2024 (actual)
- First posted
- 5 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- crossover multi-centre, double-blind, randomized control trial.
| Arm | Type | Receives |
|---|---|---|
| Experimental arm | Experimental | Diagnostic Test: Iohexol measurement, Drug: Geranylgeranylacetone (GGA), Diagnostic Test: Echocardiography, Diagnostic Test: 6-minute walking distance test, Diagnostic Test: EndoPAT, Diagnostic Test: Para-amino Hippuric Acid test, Diagnostic Test: ElectrocardiogramPatients 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. |
| Placebo arm | Placebo comparator | Diagnostic Test: Iohexol measurement, Drug: Geranylgeranylacetone (GGA), Diagnostic Test: Echocardiography, Diagnostic Test: 6-minute walking distance test, Diagnostic Test: EndoPAT, Diagnostic Test: Para-amino Hippuric Acid test, Diagnostic Test: ElectrocardiogramPatients 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. |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age≥ 50 years
- 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:
Key exclusion criteria (24 listed)
- Current acute decompensated heart failure, requiring hospitalization or augmented therapy with intravenous diuretics, vasodilators, and/or inotropic drugs
- Acute coronary syndrome, transient ischemic attack/cerebrovascular accident, major surgery within the previous 3 months
- Hemoglobin <9 g/dl at screening
- LVEF <40% measured at any time point in the history of the patient
- History of mitral valve repair or replacement
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Iohexol measurementInvasive renal hemodynamic measurement of mGFR through the administration of Iohexol. | Diagnostic test | Experimental arm, Placebo arm |
| 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. | Drug | Experimental arm, Placebo arm |
| EchocardiographyThe investigators will perform echocardiography to find changes in cardiac function. | Diagnostic test | Experimental arm, Placebo arm |
| 6-minute walking distance test6 minute walking distance test to compare exercise tolerance in participants. | Diagnostic test | Experimental arm, Placebo arm |
| EndoPATUse of EndoPAT to measure endothelial function. | Diagnostic test | Experimental arm, Placebo arm |
| Para-amino Hippuric Acid testPAH-measurement to measure ERPF. | Diagnostic test | Experimental arm, Placebo arm |
| Electrocardiogram12-lead Electrocardiogram | Diagnostic test | Experimental arm, Placebo arm |
Primary outcome
Filling pressures
Time frame: after 13 weeks of treatment
Changes in echocardiography determined filling pressures (E/e')?
Endothelial function
Time frame: after 13 weeks of treatment
Changes in EndoPAT®-derived reactive hyperemia index (RHI)
22 secondary outcomes
Left atrial volumes
Time frame: After 13 weeks of treatment
Left atrial global strain
Time frame: After 13 weeks of treatment
Left atrial emptying fractions
Time frame: After 13 weeks of treatment.
Left Ventricular global longitudinal strain
Time frame: Ater 13 weeks of treatment
Left Ventricular Myocardial relaxation
Time frame: Ater 13 weeks of treatment
Left Ventricular distensibility
Time frame: After 13 weeks of treatment
Right Ventricular systolic function
Time frame: After 13 weeks of treatment
Pulmonary Artery Pressure
Time frame: After 13 weeks of treatment
Patient reported symptoms
Time frame: After 13 weeks of treatment
Quality of life assessment
Time frame: After 13 weeks of treatment.
Functional capacity
Time frame: After 13 weeks of treatment.
CRP (inflammatory biomarker)
Time frame: After 13 weeks of treatment
Nitrosated hemoglobin (microvascular marker)
Time frame: After 13 weeks of treatment
Nitrate (microvascular marker)
Time frame: After 13 weeks of treatment
Endothelin-1 (microvascular marker)
Time frame: After 13 weeks of treatment
H2S (microvascular marker)
Time frame: After 13 weeks of treatment
Measured Glomerular Filtration Rate (mGFR)
Time frame: After 13 weeks of treatment
Effective Renal Plasma Flow (ERPF)
Time frame: After 13 weeks of treatment
Renal vascular resistance (RVR)
Time frame: After 13 weeks of treatment
Urine Albumine Creatinin Ratio
Time frame: After 13 weeks of treatment
Neutrophil gelatinase associated lipocalin (NGAL)
Time frame: After 13 weeks of treatment
Kidney Injury marker 1 (KIM-1)
Time frame: After 13 weeks of treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2025.
- Individual participant dataSharing planned: No
Related trials for Heart Failure With Preserved Ejection Fraction
Not yet recruitingPhase 2
A Study of Bimagrumab in Participants With HFpEF
Heart Failure, Diastolic, Diastolic Heart Failure
RecruitingPhase 4
The Effects of Ferric Derisomaltose in Patients With Acute Heart Failure and Iron Deficiency on Exercise Capacity and Quality of Life
Heart Failure With Preserved Ejection Fraction, Iron Deficiencies
RecruitingObservational study
Descriptive Study of Circulating Gene or Protein Inflammatory Biomarkers and Bioimpedance Parameters in a Population of Patients Hospitalized for Decompensated Heart Failure With Preserved or Mildly Reduced Cardiac Function
Inflammation Biomarkers, Heart Failure
Recruiting
Remote Rehabilitation in Patients With HFpEF (PATRON-HF)
Heart Failure With Preserved Ejection Fraction
Recruiting
ELEVATE-HFpEF Clinical Study
Heart Failure With Preserved Ejection Fraction (HFpEF)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Louis Handoko, MD, PhD principal investigator
Amsterdam University Medical Center
Adriaan Voors, MD, PhD principal investigator
University Medical Center Groningen
Loek van Heerebeek, MD, PhD principal investigator
Onze Lieve Vrouwe Gasthuis, Amsterdam
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Iohexol measurement, Geranylgeranylacetone (GGA) and Echocardiography in people with Heart Failure With Preserved Ejection Fraction, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
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 6 inclusion and 24 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: finished, as of the sponsor's last update on 1 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Filling pressures (time frame: after 13 weeks of treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 Apr 2025.