Hypertrophic CardiomyopathyPhase 2METAL-HCMNCT00500552
Perhexiline Therapy in Patients With Hypertrophic Cardiomyopathy
A Phase 2 study of Hypertrophic Cardiomyopathy, run by University Hospital Birmingham at 3 sites in United Kingdom.
Trial summary
Hypertrophic Cardiomyopathy (HCM) is a relatively common inherited heart muscle disease. Many patients experience symptoms of breathlessness, fatigue and chest pain. These symptoms are not always controlled with current therapies. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Hypertrophic Cardiomyopathy
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- 3 sitesUnited Kingdom
- Study dates
- Dec 2006to Aug 2010
- 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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Symptomatic Hypertrophic Cardiomyopathy patients
- Abnormal Peak VO2
- No significant LVOT obstruction at rest (gradient < 30mmHg)
- Sinus rhythm
Who cannot join
- Abnormal LFT.
- Concomitant use of amiodarone
- Pre-existing evidence of peripheral neuropathy.
- Women of childbearing potential.
- Patients with ICD's will be excluded from the MR part of the study
Trial locations and contacts
3 sites in 1 country.
United Kingdom3 sites
University of Birmingham
Birmingham, West Midlands, B15 2TT
heart Hospital, University College of London NHS
London, London, W1G 8PH
University of Oxford
Oxford, OX3 9DU
About this study
Official title: Metabolic Alteration With Perhexiline Therapy in Patients With Hypertrophic Cardiomyopathy (METAL-HCM Study)
Hypertrophic Cardiomyopathy (HCM) is a relatively common inherited heart muscle disease. Many patients experience symptoms of breathlessness, fatigue and chest pain. These symptoms are not always controlled with current therapies.
Recently the investigators showed that a drug called Perhexiline markedly improved exercise capacity and symptoms in patients with heart failure. In this proposal the investigators wish to test whether Perhexiline improves exercise capacity and relieves symptoms in patients with HCM
Read the detailed description
Background:
Hypertrophic cardiomyopathy (HCM) is a complex and relatively common genetic cardiac disease and it is the most common cause of sudden cardiac death in young people, including trained athletes. In a recent study using in vivo cardiac MR spectroscopy resting PCr/ATP ratio was diminished in patients with sarcomeric HCM, indicating reduced energy availability. Importantly patients with genotypic HCM who did not yet have hypertrophy had a similar degree of impairment of cardiac PCr/ATP ratio as do patients with marked hypertrophy, implying that the disturbance may be an early feature of the disease and is not simply due to the hypertrophy. In medically refractory patients with obstruction, surgical myectomy or alcohol septal ablation may be very effective. However in patients with non obstructive HCM with symptoms refractory to standard drug therapy, there are no therapeutic options (apart from cardiac transplant in very severe cases). Recently, our group showed that Perhexiline, an antianginal agent with an oxygen-sparing metabolic effect which increases the efficiency of energy production by shifting substrate utilisation from free fatty acids towards glucose, was highly effective in improving symptoms, exercise capacity (Vo2max) and cardiac function in patients with systolic heart failure of both ischaemic and non ischaemic aetiology.
Hypothesis:
The investigators postulate that Perhexiline will improve symptomatic status, peak oxygen consumption, resting and exercise diastolic function and that this will be associated with improvement in myocardial energetic status in highly symptomatic medically refractory patients with non obstructive HCM.
Methods and design:
The study is a multi-centre randomised double blind placebo controlled trial. 50 patients who meet the entry criteria and provide written informed consent will be recruited to the study. Patients will be recruited from cardiomyopathy clinics in London, Birmingham and Oxford.
The primary end point will be peak oxygen consumption (Vo2max). Secondary end points will be resting myocardial energetics (31P Cardiac MR Spectroscopy), resting and exercise diastolic function (Myocardial Nuclear studies), Symptomatic Status (Minnesota questionnaire)and LV function (Speckle Tracking Echo measurements).
After the investigations have been performed, subjects will be randomised to receive either 100 mg of Perhexiline a day or placebo for 3 months. Following completions of three months therapy, these investigations will be repeated.
- Conditions
- Hypertrophic Cardiomyopathy
- Being tested
- Perhexiline/Placebo
- Keywords
- Perhexiline, Hypertrophic Cardiomyopathy
- Medical subject headings
- Cardiomyopathy, Hypertrophic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Perhexiline/PlaceboDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Peak oxygen consumption (Vo2max)
Measured: 3-4 months
Secondary outcomes (4)
LV function (TDI and 2DS Echo)
Measured: 3-4 months
Symptomatic Status (questionnaire)
Measured: 3-4 months
Resting myocardial energetics (31P Cardiac MR Spectroscopy)
Measured: 3-4 months
Diastolic function at rest and during exercise (Nuclear studies)
Measured: 3-4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2007 (estimated)
- Study startDec 2006
- Primary completionAug 2010
- Study completionAug 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hypertrophic CardiomyopathyStudies 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
- Double blind
- Enrolment
- 44 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- British Heart Foundation, University College London Hospitals, University of Oxford
- Investigators
- Michael Frenneaux, MD, Principal investigator, University of Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00500552
- Sponsor's protocol ID
- RRK 2848, 05/Q2707/325
- Other IDs
- PG/05/087
- Acronym
- METAL-HCM
- Status last verified
- Aug 2010
- First submitted
- 10 Jul 2007
- Last updated
- 4 Nov 2010
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Abozguia K, Elliott P, McKenna W, Phan TT, Nallur-Shivu G, Ahmed I, Maher AR, Kaur K, Taylor J, Henning A, Ashrafian H, Watkins H, Frenneaux M. Metabolic modulator perhexiline corrects energy deficiency and improves exercise capacity in symptomatic hypertrophic cardiomyopathy. Circulation. 2010 Oct 19;122(16):1562-9. doi: 10.1161/CIRCULATIONAHA.109.934059. Epub 2010 Oct 4.
PubMed 20921440
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metabolic Alteration With Perhexiline Therapy in Patients With Hypertrophic Cardiomyopathy (METAL-HCM Study)
- ClinicalTrials.gov ID
- NCT00500552
- Acronym / sponsor ID
- METAL-HCM / RRK 2848, 05/Q2707/325
- Conditions
- Hypertrophic Cardiomyopathy
- Keywords
- Perhexiline, Hypertrophic Cardiomyopathy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (estimated)
- Lead sponsor
- University Hospital BirminghamUniversity, hospital or other
- Collaborators
- British Heart Foundation, University College London Hospitals, University of Oxford
- Study start
- Dec 2006
- Primary completion
- Aug 2010 (actual)
- Study completion
- Aug 2010 (actual)
- First posted
- 12 Jul 2007 (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.
Hypertrophic Cardiomyopathy (HCM) is a relatively common inherited heart muscle disease. Many patients experience symptoms of breathlessness, fatigue and chest pain. These symptoms are not always controlled with current therapies.
Recently the investigators showed that a drug called Perhexiline markedly improved exercise capacity and symptoms in patients with heart failure. In this proposal the investigators wish to test whether Perhexiline improves exercise capacity and relieves symptoms in patients with HCM
Detailed description
Background:
Hypertrophic cardiomyopathy (HCM) is a complex and relatively common genetic cardiac disease and it is the most common cause of sudden cardiac death in young people, including trained athletes. In a recent study using in vivo cardiac MR spectroscopy resting PCr/ATP ratio was diminished in patients with sarcomeric HCM, indicating reduced energy availability. Importantly patients with genotypic HCM who did not yet have hypertrophy had a similar degree of impairment of cardiac PCr/ATP ratio as do patients with marked hypertrophy, implying that the disturbance may be an early feature of the disease and is not simply due to the hypertrophy. In medically refractory patients with obstruction, surgical myectomy or alcohol septal ablation may be very effective. However in patients with non obstructive HCM with symptoms refractory to standard drug therapy, there are no therapeutic options (apart from cardiac transplant in very severe cases). Recently, our group showed that Perhexiline, an antianginal agent with an oxygen-sparing metabolic effect which increases the efficiency of energy production by shifting substrate utilisation from free fatty acids towards glucose, was highly effective in improving symptoms, exercise capacity (Vo2max) and cardiac function in patients with systolic heart failure of both ischaemic and non ischaemic aetiology.
Hypothesis:
The investigators postulate that Perhexiline will improve symptomatic status, peak oxygen consumption, resting and exercise diastolic function and that this will be associated with improvement in myocardial energetic status in highly symptomatic medically refractory patients with non obstructive HCM.
Methods and design:
The study is a multi-centre randomised double blind placebo controlled trial. 50 patients who meet the entry criteria and provide written informed consent will be recruited to the study. Patients will be recruited from cardiomyopathy clinics in London, Birmingham and Oxford.
The primary end point will be peak oxygen consumption (Vo2max). Secondary end points will be resting myocardial energetics (31P Cardiac MR Spectroscopy), resting and exercise diastolic function (Myocardial Nuclear studies), Symptomatic Status (Minnesota questionnaire)and LV function (Speckle Tracking Echo measurements).
After the investigations have been performed, subjects will be randomised to receive either 100 mg of Perhexiline a day or placebo for 3 months. Following completions of three months therapy, these investigations will be repeated.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Symptomatic Hypertrophic Cardiomyopathy patients
- Abnormal Peak VO2
- No significant LVOT obstruction at rest (gradient < 30mmHg)
- Sinus rhythm
Key exclusion criteria (5 listed)
- Abnormal LFT.
- Concomitant use of amiodarone
- Pre-existing evidence of peripheral neuropathy.
- Women of childbearing potential.
- Patients with ICD's will be excluded from the MR part of the study
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 |
|---|---|---|
| Perhexiline/Placebo | Drug | – |
Primary outcome
Peak oxygen consumption (Vo2max)
Time frame: 3-4 months
4 secondary outcomes
LV function (TDI and 2DS Echo)
Time frame: 3-4 months
Symptomatic Status (questionnaire)
Time frame: 3-4 months
Resting myocardial energetics (31P Cardiac MR Spectroscopy)
Time frame: 3-4 months
Diastolic function at rest and during exercise (Nuclear studies)
Time frame: 3-4 months
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 4 Nov 2010.
- Derived from this study: PubMed 20921440Abozguia K, Elliott P, McKenna W, Phan TT, Nallur-Shivu G, Ahmed I, Maher AR, Kaur K, Taylor J, Henning A, Ashrafian H, Watkins H, Frenneaux M. Metabolic modulator perhexiline corrects energy deficiency and improves exercise capacity in symptomatic hypertrophic cardiomyopathy. Circulation. 2010 Oct 19;122(16):1562-9. doi: 10.1161/CIRCULATIONAHA.109.934059. Epub 2010 Oct 4.
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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 Frenneaux, MD principal investigator
University of Birmingham
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study of Hypertrophic Cardiomyopathy, run by University Hospital Birmingham at 3 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 4 inclusion and 5 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 4 Nov 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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. 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?
Peak oxygen consumption (Vo2max) (time frame: 3-4 months). 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 NCT00500552, which also lists 1 linked publication.
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 4 Nov 2010.