Becker Muscular DystrophyPhase 2NCT01350154
Effect of Modulating the nNOS System on Cardiac, Muscular and Cognitive Function in Becker Muscular Dystrophy Patients
A Phase 2 study testing Sildenafil in people with Becker Muscular Dystrophy, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.
Trial summary
This study is done to evaluate whether treatment with the drug sildenafil (Revatio®) can improve muscular, cardiac, cerebrovascular or cognitive function in patients with Beckers muscular dystrophy when compared to placebo (inactive medication). Read more about this study
- Who is it for?
- Ages 18 to 80 years, men only
- Conditions the study is for
- Becker Muscular Dystrophy
- What is being tested?
- Sildenafil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 17 participants
- Where
- 1 siteDenmark
- Study dates
- Nov 2011to Apr 2013
- 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
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Muscular dystrophy with known deficiency in nNOS
- Reduced cardiac function (<50%) and/or reduced muscular function (MRC<4+)
- Stable dosing (> 3 month)of cardiovascular medication
- Signed informed consent
Who cannot join
- Recent (< 6 month) cerebral or cardiac stroke
- Use of nitrate containing compounds, alpha receptor blocking agents or potent CUP3A4 inhibitors.
- Intolerance or allergy to sildenafil, or intake of drugs not compatible with sildenafil intake
- Overuse of drugs or alcohol
- inclusion in other trials of experimental medication within last 30 days
- known epilepsy
Show all 11Show fewer
- reduced liver function (ASAT >500U/l in 2 repeated measurements when corrected for increase in creatinkinase levels.
- non-arteriitis anterior ischemic optic neuropathy (NAION) with reduced vision
- contraindications for MRI scan (metal implants, claustrophobia)
- hypotension (<90 mmHg systolic at baseline)
- conditions, medical or psychosocial which makes the subject inclusion inadvisable
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Neuromuscular Clinic and Research Unit, Dept. Neurology, Rigshospitalet,
Copenhagen, 2100
About this study
Official title: Does Modulation of the nNOS System in Patients With Muscular Dystrophy and Defect nNOS Signalling Affect Cardiac, Muscular or Cognitive Function?
This study is done to evaluate whether treatment with the drug sildenafil (Revatio®) can improve muscular, cardiac, cerebrovascular or cognitive function in patients with Beckers muscular dystrophy when compared to placebo (inactive medication). The study is based on the recent findings of an improved cardiac function in a mouse model of muscular dystrophy (Adamo et al 2010) and the previous findings of changed cognitive function in people with Becker dystrophy.
In muscular dystrophy, the cellular protein, dystrophin is affected. During normal conditions, the enzyme neuronal nitric oxide synthase (nNOS), which produce nitric oxide (NO), is attached to dystrophin. NO is important in normal vascular function in each of muscle, heart and brain by stimulating production of cyclic GMP. However, in muscular dystrophy with dystrophin deficiency, nNOS do not have the normal cellular anchor, resulting in decreased NO levels and subsequent reduced cyclic GMP production. Sildenafil inhibits degradation of cGMP thus prolonging and increasing a cGMP response. Such effects are the basis for use of sildenafil in pulmonary hypertension and erectile dysfunction. Current hypothesis: Sildenafil restores the cyclic GMP function affected in muscular dystrophy wit nNOS deficiency resulting in improved muscle, cardiac, cerebrovascular and cognitive function.
Read the detailed description
The current clinical trial including people with Becker's muscular dystrophy and established deficiency in muscular content of nNOS protein consist of three sub-studies focusing on each of muscle function, cardiac function and brain function. In muscular dystrophy the dystrophin cellular complex usually located to muscle cells, is disrupted resulting in a known reduced nNOS activity. The reduced nNOS leads to reduced cyclic GMP production. nNOS and cyclic GMP are involved in the vascular response in striate muscle, cardiac vessels as well as the cerebrovascular response to hypercapnia and regional activation. In muscular dystrophy, the is an affected muscular and cardiac function and in some patients a changed cognitive function in described. Whether such is related to a reduced nNOS function and subsequent cGMP production is not fully understood. Inhibition of cGMP degradation by inhibiting the cGMP degrading enzyme phosphodiesterase 5 (PDE5) using PDE5 inhibitors such as sildenafil may result in restoration of vascular responses.
The study is designed as a double blind, randomised, balanced, placebo-controlled cross-over study performed during a 10 week treatment period. The patients will receive 4 weeks of either sildenafil or placebo with a 2 week washout period in between treatments. The study out-come parameters will be performed on two consecutive days at baseline, 4 weeks and 10 weeks, at two collaborating centers, Rigshospitalet for muscle and cardiac parameters and Glostrup Hospital for cerebrovascular and cognitive parameters.
The primary endpoints relate to each sub-study, assessing and comparing individual changes from baseline and during placebo/sildenafil treatment.
- Conditions
- Becker Muscular Dystrophy
- Being tested
- Sildenafil, Placebo
- Keywords
- clinical trial, sildenafil, revatio, muscular dystrophy, adult, nNOS
- Medical subject headings
- Muscular Dystrophy, Duchenne, Muscular Dystrophies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SildenafilDrug
Also called Placebo
20 mg in gelatine capsules, oral, three times daily
PlaceboDrug
Also called Sildenafil (Revatio)
Lactose monohydrate oral in gelatine capsules, 3 times daily
| Study group | Role | What they receive |
|---|---|---|
| Sildenafil (Revation) 20 mg | Experimental | This arm will receive sildenafil for 4 weeks followed by 2 weeks washout and 4 weeks placebo. Receives: Drug: Sildenafil |
| Placebo | Experimental | This arm will receive placebo for 4 weeks followed by 2 weeks washout and 4 weeks sildenafil Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in change from baseline to 4 week placebo/sildenafil treatment in handgrip test with concomitant ultrasound measurement of flow in the brachial artery
Primary outcome for substudy 1
Measured: Baseline and 4 weeks treatment
Difference in changes from baseline to 4 week placebo/sildenafil treatment in resting cardiac end-diastolic volume measured by MRI
Primary outcome for substudy 2
Measured: Baseline and 4 week treatment
Difference in changes from baseline to 4 week placebo/sildenafil treatment in cerebrovascular reactivity to CO2 inhalation and finger stimulation measured by BOLD fMRI
Primary outcome for substudy 3
Measured: Baseline and 4 weeks treatment
Difference in changes from baseline to 4 weeks placebo/sildenafil treatment in Cognitive function measured by Cambridge Neuropsychological Test Automated Battery (CANTAB)
Primay outcome for substudy 3
Measured: Baseline and 4 weeks treatment
Secondary outcomes (9)
Difference in changes from baseline to 4 weeks placebo/sildenafil treatment in 6 minutes walk test
Substudy 1
Measured: Baseline and 4 weeks treatment
Difference in changes from baseline to 4 weeks placebo/sildenafil treatment in max test, measured by O2 uptake during maximal exercise on bike
Substudy 1
Measured: Baseline and 4 weeks treatment
Difference in changes from baseline to 4 weeks placebo/sildenafil treatment in Quality of life by SF36
Substudy 1
Measured: Baseline and 4 weeks treatment
Difference in changes from baseline to 4 weeks placebo/sildenafil treatment in resting cardiac function measured by cardiac MRI
Substudy 2. Evaluation of resting cardiac ejection fraction and end-systolic volume.
Measured: Baseline and 4 weeks treatment
Difference in changes from baseline to 4 weeks placebo/sildenafil treatment in cardiac function during hand grip exercise measured by cardiac MRI
Substudy 2. Cardiac volumes and ejection fraction during 1 minute repeated maximal force hand exercise will be measured.
Measured: Baseline and 4 weeks treatment
Difference in changes from baseline to 4 weeks placebo/sildenafil treatment in cerebrovascular reactivity and blood flow
Substudy 3. fMRI BOLD evaluation of visual stimulation, MRI angiography for arterial diameter, arterial spin labeling for evaluation of cerebral blood flow and blood volumen.
Measured: Baseline and 4 weeks treatment
Difference in changes from baseline to 4 weeks placebo/sildenafil treatment in basic activity and metabolites of the brain
Substudy 3.Resting state network by fMRI and metabolites in brain regions by MRI spectroskopy.
Measured: Baseline and 4 weeks treatment
Difference in changes from baseline to 4 weeks placebo/sildenafil treatment in cognitive function measured by paper and pen test battery
Substudy 3. A paper and pen cognitive test battery will be applied, including Trail making A and B, Addenbrooke's Cognitive Examination, Symbol DIgital MOdality tests
Measured: Baseline and 4 weeks treatment
Difference in changes from baseline to 4 weeks treatment placebo/sildenafil in plasma levels of signalling molecules
Substudy 3. From blood samples taken at baseline, 4 and 10 weeks, analysis of several signalling molecules relevant for cardiac and cerebrovascular function will be performed.
Measured: Baseline and 4 weeks treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2011 (estimated)
- Study startNov 2011
- Primary completionApr 2013
- Study completionApr 2013
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 Becker Muscular DystrophyStudies of the same condition, open and under way.
- More trials run by Copenhagen University Hospital, RigshospitaletThe 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
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Copenhagen University Hospital, Rigshospitalet
- Sponsor type
- University, hospital or other
- Collaborators
- Glostrup University Hospital, Copenhagen
- Responsible party
- Principal investigator, Christina Kruuse, Copenhagen University Hospital, Rigshospitalet
- Investigators
- John Vissing, MD, DMSci, Study chair, Neuromuscular Clinic and Research Unit, Dept. Neurology, Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01350154
- Sponsor's protocol ID
- RHGLBMD
- Status last verified
- Apr 2013
- First submitted
- 4 May 2011
- Last updated
- 10 Apr 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Mickle AT, Johnston KM, Ricchetti-Masterson KL, Kennedy AR, Korpach SG, Gooch KL. The natural history of Becker muscular dystrophy: A systematic literature review. J Neuromuscul Dis. 2026 Feb 1:22143602261420045. doi: 10.1177/22143602261420045. Online ahead of print.
PubMed 41671094
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Does Modulation of the nNOS System in Patients With Muscular Dystrophy and Defect nNOS Signalling Affect Cardiac, Muscular or Cognitive Function?
- ClinicalTrials.gov ID
- NCT01350154
- Acronym / sponsor ID
- RHGLBMD
- Conditions
- Becker Muscular Dystrophy
- Keywords
- clinical trial, sildenafil, revatio, muscular dystrophy, adult, nNOS
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Copenhagen University Hospital, RigshospitaletUniversity, hospital or other
- Collaborators
- Glostrup University Hospital, Copenhagen
- Study start
- Nov 2011
- Primary completion
- Apr 2013 (actual)
- Study completion
- Apr 2013 (actual)
- First posted
- 9 May 2011 (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.
This study is done to evaluate whether treatment with the drug sildenafil (Revatio®) can improve muscular, cardiac, cerebrovascular or cognitive function in patients with Beckers muscular dystrophy when compared to placebo (inactive medication). The study is based on the recent findings of an improved cardiac function in a mouse model of muscular dystrophy (Adamo et al 2010) and the previous findings of changed cognitive function in people with Becker dystrophy.
In muscular dystrophy, the cellular protein, dystrophin is affected. During normal conditions, the enzyme neuronal nitric oxide synthase (nNOS), which produce nitric oxide (NO), is attached to dystrophin. NO is important in normal vascular function in each of muscle, heart and brain by stimulating production of cyclic GMP. However, in muscular dystrophy with dystrophin deficiency, nNOS do not have the normal cellular anchor, resulting in decreased NO levels and subsequent reduced cyclic GMP production. Sildenafil inhibits degradation of cGMP thus prolonging and increasing a cGMP response. Such effects are the basis for use of sildenafil in pulmonary hypertension and erectile dysfunction. Current hypothesis: Sildenafil restores the cyclic GMP function affected in muscular dystrophy wit nNOS deficiency resulting in improved muscle, cardiac, cerebrovascular and cognitive function.
Detailed description
The current clinical trial including people with Becker's muscular dystrophy and established deficiency in muscular content of nNOS protein consist of three sub-studies focusing on each of muscle function, cardiac function and brain function. In muscular dystrophy the dystrophin cellular complex usually located to muscle cells, is disrupted resulting in a known reduced nNOS activity. The reduced nNOS leads to reduced cyclic GMP production. nNOS and cyclic GMP are involved in the vascular response in striate muscle, cardiac vessels as well as the cerebrovascular response to hypercapnia and regional activation. In muscular dystrophy, the is an affected muscular and cardiac function and in some patients a changed cognitive function in described. Whether such is related to a reduced nNOS function and subsequent cGMP production is not fully understood. Inhibition of cGMP degradation by inhibiting the cGMP degrading enzyme phosphodiesterase 5 (PDE5) using PDE5 inhibitors such as sildenafil may result in restoration of vascular responses.
The study is designed as a double blind, randomised, balanced, placebo-controlled cross-over study performed during a 10 week treatment period. The patients will receive 4 weeks of either sildenafil or placebo with a 2 week washout period in between treatments. The study out-come parameters will be performed on two consecutive days at baseline, 4 weeks and 10 weeks, at two collaborating centers, Rigshospitalet for muscle and cardiac parameters and Glostrup Hospital for cerebrovascular and cognitive parameters.
The primary endpoints relate to each sub-study, assessing and comparing individual changes from baseline and during placebo/sildenafil treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sildenafil (Revation) 20 mg | Experimental | Drug: SildenafilThis arm will receive sildenafil for 4 weeks followed by 2 weeks washout and 4 weeks placebo. |
| Placebo | Experimental | Drug: PlaceboThis arm will receive placebo for 4 weeks followed by 2 weeks washout and 4 weeks sildenafil |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Muscular dystrophy with known deficiency in nNOS
- Reduced cardiac function (<50%) and/or reduced muscular function (MRC<4+)
- Stable dosing (> 3 month)of cardiovascular medication
- Signed informed consent
Key exclusion criteria (11 listed)
- Recent (< 6 month) cerebral or cardiac stroke
- Use of nitrate containing compounds, alpha receptor blocking agents or potent CUP3A4 inhibitors.
- Intolerance or allergy to sildenafil, or intake of drugs not compatible with sildenafil intake
- Overuse of drugs or alcohol
- inclusion in other trials of experimental medication within last 30 days
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 |
|---|---|---|
| SildenafilAlso: Placebo20 mg in gelatine capsules, oral, three times daily | Drug | Sildenafil (Revation) 20 mg |
| PlaceboAlso: Sildenafil (Revatio)Lactose monohydrate oral in gelatine capsules, 3 times daily | Drug | Placebo |
Primary outcome
Difference in change from baseline to 4 week placebo/sildenafil treatment in handgrip test with concomitant ultrasound measurement of flow in the brachial artery
Time frame: Baseline and 4 weeks treatment
Primary outcome for substudy 1
Difference in changes from baseline to 4 week placebo/sildenafil treatment in resting cardiac end-diastolic volume measured by MRI
Time frame: Baseline and 4 week treatment
Primary outcome for substudy 2
Difference in changes from baseline to 4 week placebo/sildenafil treatment in cerebrovascular reactivity to CO2 inhalation and finger stimulation measured by BOLD fMRI
Time frame: Baseline and 4 weeks treatment
Primary outcome for substudy 3
Difference in changes from baseline to 4 weeks placebo/sildenafil treatment in Cognitive function measured by Cambridge Neuropsychological Test Automated Battery (CANTAB)
Time frame: Baseline and 4 weeks treatment
Primay outcome for substudy 3
9 secondary outcomes
Difference in changes from baseline to 4 weeks placebo/sildenafil treatment in 6 minutes walk test
Time frame: Baseline and 4 weeks treatment
Difference in changes from baseline to 4 weeks placebo/sildenafil treatment in max test, measured by O2 uptake during maximal exercise on bike
Time frame: Baseline and 4 weeks treatment
Difference in changes from baseline to 4 weeks placebo/sildenafil treatment in Quality of life by SF36
Time frame: Baseline and 4 weeks treatment
Difference in changes from baseline to 4 weeks placebo/sildenafil treatment in resting cardiac function measured by cardiac MRI
Time frame: Baseline and 4 weeks treatment
Difference in changes from baseline to 4 weeks placebo/sildenafil treatment in cardiac function during hand grip exercise measured by cardiac MRI
Time frame: Baseline and 4 weeks treatment
Difference in changes from baseline to 4 weeks placebo/sildenafil treatment in cerebrovascular reactivity and blood flow
Time frame: Baseline and 4 weeks treatment
Difference in changes from baseline to 4 weeks placebo/sildenafil treatment in basic activity and metabolites of the brain
Time frame: Baseline and 4 weeks treatment
Difference in changes from baseline to 4 weeks placebo/sildenafil treatment in cognitive function measured by paper and pen test battery
Time frame: Baseline and 4 weeks treatment
Difference in changes from baseline to 4 weeks treatment placebo/sildenafil in plasma levels of signalling molecules
Time frame: Baseline and 4 weeks 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 10 Apr 2013.
- Derived from this study: PubMed 41671094Mickle AT, Johnston KM, Ricchetti-Masterson KL, Kennedy AR, Korpach SG, Gooch KL. The natural history of Becker muscular dystrophy: A systematic literature review. J Neuromuscul Dis. 2026 Feb 1:22143602261420045. doi: 10.1177/22143602261420045. Online ahead of print.
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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.
John Vissing, MD, DMSci study chair
Neuromuscular Clinic and Research Unit, Dept. Neurology, Rigshospitalet
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 Sildenafil in people with Becker Muscular Dystrophy, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.
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 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 10 Apr 2013. 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 Denmark. 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?
Difference in change from baseline to 4 week placebo/sildenafil treatment in handgrip test with concomitant ultrasound measurement of flow in the brachial artery (time frame: Baseline and 4 weeks treatment). The study lists 4 primary outcomes in all. 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 NCT01350154, 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 10 Apr 2013.