Effect of Modulating the nNOS System on Cardiac, Muscular and Cognitive Function in Becker Muscular Dystrophy Patients

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT01350154
• Date of registration: 04/05/2011
• Prospective Registration: Yes
• Primary sponsor: Rigshospitalet, Denmark
• Public title: Effect of Modulating the nNOS System on Cardiac, Muscular and Cognitive Function in Becker Muscular Dystrophy Patients
• Scientific title: Does Modulation of the nNOS System in Patients With Muscular Dystrophy and Defect nNOS Signalling Affect Cardiac, Muscular or Cognitive Function?
• Date of first enrolment: November 2011
• Target sample size: 17
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT01350154
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
• Phase: Phase 2

Countries of recruitment

Denmark

Contacts

• Name: John Vissing, MD, DMSci
• Affiliation: Neuromuscular Clinic and Research Unit, Dept. Neurology, Rigshospitalet

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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

Exclusion Criteria:

- 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

- 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



Age minimum: 18 Years
Age maximum: 80 Years
Gender: Male

Health Condition(s) or Problem(s) studied

Becker Muscular Dystrophy

Intervention(s)

Drug: Sildenafil

Drug: Placebo

Primary Outcome(s)

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]

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]

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]

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]

Secondary Outcome(s)

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 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 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 6 minutes walk test [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 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 resting cardiac function measured by cardiac MRI [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]

Secondary ID(s)

RHGLBMD

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Glostrup University Hospital, Copenhagen