Chronic Heart FailurePhase 2NCT00841139
Metabolic Manipulation in Chronic Heart Failure
A Phase 2 study testing Perhexiline in people with Chronic Heart Failure, run by University Hospital Birmingham NHS Foundation Trust at 2 sites in United Kingdom.
Trial summary
Conventional measures used for the treatment of chronic heart failure act predominantly by reducing the work performed by the heart. In a recent study, the investigators showed that one drug (perhexiline) substantially improved symptoms and cardiac function in heart failure. Read more about this study
- Who is it for?
- Ages 16 to 90 years
- Conditions the study is for
- Chronic Heart Failure
- What is being tested?
- Perhexiline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- Feb 2009to Sep 2011
- 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 16 to 90 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Optimally-medicated idiopathic dilated cardiomyopathy
- Symptomatic ( NYHA IIb-III)
- Impaired left ventricular systolic function (EF < 40%)
Who cannot join
- Abnormal liver function tests (defined as above twice the upper limit of normal (ULN))
- Concomitant use of Amiodarone , Quinidine , Haloperidol or Selective serotonin (5HT) uptake inhibitors such as Fluoxetine and Paroxetine which may inhibit the CYP2D6 enzyme.
- Pre-existing evidence of peripheral neuropathy.
- Women of childbearing potential.
- Patients with implantable cardiac devices (or any other contraindication to MRI).
- Obesity ( BMI > 32)
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- Obstructive sleep apnea syndrome
- Patients with known hypersensitivity to perhexiline
- Patients with impaired renal function (Creatinine > 250 µmol/L)
- Valvular heart disease defined as more than moderate valvular stenosis or regurgitation.
- Atrial Fibrillation
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites
University Hospitals Brimingham NHS Foundation Trust
Birmingham, West Midlands, B15 2TH
University of Birmingham
Birmingham, West Midlands, B15 2TT
About this study
Conventional measures used for the treatment of chronic heart failure act predominantly by reducing the work performed by the heart. In a recent study, the investigators showed that one drug (perhexiline) substantially improved symptoms and cardiac function in heart failure. The investigators wish to confirm these findings and test whether or not this drug acts by altering the heart's energy source thus augmenting the energetic status and work efficiency of the heart.
Read the detailed description
Perhexiline maleate is an antianginal agent which increases the efficiency of energy production by shifting substrate utilisation from free fatty acids towards glucose. We showed that perhexiline therapy was highly effective in improving exercise capacity, symptoms and cardiac function in patients with systolic heart failure of both ischaemic and non ischaemic aetiology. Perhexiline acts by inhibiting both carnitine palmitoyl transferase-1 (CPT-1) and CPT-2, which are key enzymes in mitochondrial free fatty acid uptake. This leads to increased myocardial glucose substrate utilization. Further we wish to ascertain whether or not this drug improves cardiac energetics and efficiency by altering substrate utilization. In this proposal we will assess the cardiac function (by cardiac Magnetic Resonance Imaging MRI), cardiac energetic status (by cardiac Magnetic Resonance Spectroscopy MRS), cardiac efficiency (via pressure-volume loops) and substrate utilization (via left and right heart catheterization), following one month of perhexiline therapy or placebo in patients with symptomatic idiopathic dilated cardiomyopathy on optimal conventional heart failure medications. An interim analysis is planned after 20 patients.
- Conditions
- Chronic Heart Failure
- Being tested
- Perhexiline, Placebo
- Keywords
- perhexiline, idiopathic dilated cardiomyopathy, magnetic resonance spectroscopy, cardiac energetics
- Medical subject headings
- Cardiomyopathy, Dilated
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PerhexilineDrug
Also called Pexsig
100mg o bd
PlaceboDrug
1 tablet bd
| Study group | Role | What they receive |
|---|---|---|
| Perhexiline | Experimental | perhexiline 100mg bd for 1 month duration Receives: Drug: Perhexiline |
| Placebo | Placebo comparator | placebo one tablet bd for 1 month duration Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in cardiac energetics as demonstrated by resting myocardial PCr/ATP ratio from cardiac MRS
Measured: 1 Month
Secondary outcomes (2)
Change in mechanical efficiency (external work / MVO2)
Measured: 1 Month
Change in respiratory quotient
Measured: 1 Month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2009 (estimated)
- Study startFeb 2009
- Primary completionSep 2011
- Study completionSep 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Chronic Heart FailureStudies of the same condition, open and under way.
- 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
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Birmingham NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- British Heart Foundation
- Responsible party
- Principal investigator, Roger Beadle, University Hospital Birmingham NHS Foundation Trust
- Investigators
- Michael P Frenneaux, MBBS MD, Principal investigator, University of BirminghamRoger M Beadle, MBBS, Study director, University of Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00841139
- Sponsor's protocol ID
- 2004-004965-14
- Other IDs
- MREC: 06/Q2707/7, R&D Birminham: RRK 2785, MHRA: 21761/0003/001, 2004-004965-14, 2004
- Status last verified
- Nov 2011
- First submitted
- 6 Feb 2009
- Last updated
- 29 Nov 2011
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Beadle RM, Williams LK, Kuehl M, Bowater S, Abozguia K, Leyva F, Yousef Z, Wagenmakers AJ, Thies F, Horowitz J, Frenneaux MP. Improvement in cardiac energetics by perhexiline in heart failure due to dilated cardiomyopathy. JACC Heart Fail. 2015 Mar;3(3):202-11. doi: 10.1016/j.jchf.2014.09.009. Epub 2015 Jan 28.
PubMed 25650370Beadle RM, Williams LK, Abozguia K, Patel K, Leon FL, Yousef Z, Wagenmakers A, Frenneaux MP. Metabolic manipulation in chronic heart failure: study protocol for a randomised controlled trial. Trials. 2011 Jun 6;12:140. doi: 10.1186/1745-6215-12-140.
PubMed 21645332
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metabolic Manipulation in Chronic Heart Failure
- ClinicalTrials.gov ID
- NCT00841139
- Acronym / sponsor ID
- 2004-004965-14
- Conditions
- Chronic Heart Failure
- Keywords
- perhexiline, idiopathic dilated cardiomyopathy, magnetic resonance spectroscopy, cardiac energetics
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- University Hospital Birmingham NHS Foundation TrustUniversity, hospital or other
- Collaborators
- British Heart Foundation
- Study start
- Feb 2009
- Primary completion
- Sep 2011 (actual)
- Study completion
- Sep 2011 (actual)
- First posted
- 11 Feb 2009 (estimated)
- 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.
Conventional measures used for the treatment of chronic heart failure act predominantly by reducing the work performed by the heart. In a recent study, the investigators showed that one drug (perhexiline) substantially improved symptoms and cardiac function in heart failure. The investigators wish to confirm these findings and test whether or not this drug acts by altering the heart's energy source thus augmenting the energetic status and work efficiency of the heart.
Detailed description
Perhexiline maleate is an antianginal agent which increases the efficiency of energy production by shifting substrate utilisation from free fatty acids towards glucose. We showed that perhexiline therapy was highly effective in improving exercise capacity, symptoms and cardiac function in patients with systolic heart failure of both ischaemic and non ischaemic aetiology. Perhexiline acts by inhibiting both carnitine palmitoyl transferase-1 (CPT-1) and CPT-2, which are key enzymes in mitochondrial free fatty acid uptake. This leads to increased myocardial glucose substrate utilization. Further we wish to ascertain whether or not this drug improves cardiac energetics and efficiency by altering substrate utilization. In this proposal we will assess the cardiac function (by cardiac Magnetic Resonance Imaging MRI), cardiac energetic status (by cardiac Magnetic Resonance Spectroscopy MRS), cardiac efficiency (via pressure-volume loops) and substrate utilization (via left and right heart catheterization), following one month of perhexiline therapy or placebo in patients with symptomatic idiopathic dilated cardiomyopathy on optimal conventional heart failure medications. An interim analysis is planned after 20 patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Perhexiline | Experimental | Drug: Perhexilineperhexiline 100mg bd for 1 month duration |
| Placebo | Placebo comparator | Drug: Placeboplacebo one tablet bd for 1 month duration |
Who may qualify
- Ages
- 16 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Optimally-medicated idiopathic dilated cardiomyopathy
- Symptomatic ( NYHA IIb-III)
- Impaired left ventricular systolic function (EF < 40%)
Key exclusion criteria (11 listed)
- Abnormal liver function tests (defined as above twice the upper limit of normal (ULN))
- Concomitant use of Amiodarone , Quinidine , Haloperidol or Selective serotonin (5HT) uptake inhibitors such as Fluoxetine and Paroxetine which may inhibit the CYP2D6 enzyme.
- Pre-existing evidence of peripheral neuropathy.
- Women of childbearing potential.
- Patients with implantable cardiac devices (or any other contraindication to MRI).
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 |
|---|---|---|
| PerhexilineAlso: Pexsig100mg o bd | Drug | Perhexiline |
| Placebo1 tablet bd | Drug | Placebo |
Primary outcome
Change in cardiac energetics as demonstrated by resting myocardial PCr/ATP ratio from cardiac MRS
Time frame: 1 Month
2 secondary outcomes
Change in mechanical efficiency (external work / MVO2)
Time frame: 1 Month
Change in respiratory quotient
Time frame: 1 Month
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 29 Nov 2011.
- Derived from this study: PubMed 25650370Beadle RM, Williams LK, Kuehl M, Bowater S, Abozguia K, Leyva F, Yousef Z, Wagenmakers AJ, Thies F, Horowitz J, Frenneaux MP. Improvement in cardiac energetics by perhexiline in heart failure due to dilated cardiomyopathy. JACC Heart Fail. 2015 Mar;3(3):202-11. doi: 10.1016/j.jchf.2014.09.009. Epub 2015 Jan 28.
- Derived from this study: PubMed 21645332Beadle RM, Williams LK, Abozguia K, Patel K, Leon FL, Yousef Z, Wagenmakers A, Frenneaux MP. Metabolic manipulation in chronic heart failure: study protocol for a randomised controlled trial. Trials. 2011 Jun 6;12:140. doi: 10.1186/1745-6215-12-140.
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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.
Michael P Frenneaux, MBBS MD principal investigator
University of Birmingham
Roger M Beadle, MBBS study director
University of Birmingham
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Perhexiline in people with Chronic Heart Failure, run by University Hospital Birmingham NHS Foundation Trust at 2 sites in United Kingdom.
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 11 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 29 Nov 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. 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?
Change in cardiac energetics as demonstrated by resting myocardial PCr/ATP ratio from cardiac MRS (time frame: 1 Month). 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 NCT00841139, which also lists 2 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 29 Nov 2011.