Please select the eligibility criteria that correspond to the clinical trial below.
Title: Compare Efficacy of the Angiotensin Converting Enzyme Inhibitor (ACEi) Lisinopril With Angiotensin II Receptor Antagonist Losartan (ARB) for the Cardiomyopathy of Duchenne Muscular Dystrophy
Brief Summary: This trial is a double-blind randomized clinical trial of lisinopril versus losartan for the treatment of cardiomyopathy in Duchenne Muscular Dystrophy (DMD). Both drugs are known to be effective for the treatment of dilated cardiomyopathy. ACEi have been reported to delay the onset and progression of left ventricle dysfunction in children with DMD. Multiple studies show therapeutic efficacy of losartan in animals with cardiomyopathy related to muscular dystrophy and in patients with cardiomyopathy from diverse causes. ARBs are often reserved for patients in whom heart failure is not adequately treated or where side effects preclude the use of an ACEi. However, in DMD, losartan might be a better choice as a first line drug because of studies demonstrating a potential benefit for skeletal muscle in the mdx mouse. Considering that both skeletal and cardiac muscles are major contributors of the disability of DMD, a drug that could improve both heart and skeletal muscles simultaneously would need consideration as the drug of choice for the cardiomyopathic DMD patient.


Options:
A: Inclusion Criteria:

* Ambulant subjects with Duchenne muscular dystrophy resulting from a mutation in the DMD gene, confirmed by a state-of-the-art DNA diagnostic technique covering all DMD gene exons, including but not limited to MLPA (Multiplex Ligation-dependent Probe Amplification), CGH (Comparative Genomic Hybridisation) or H-RMCA (High-Resolution Melting Curve Analysis), and correctable by GSK2402968-induced DMD exon 51 skipping,
* Males, at least 5 years of age and with a life expectancy of at least 1 year
* Able to rise from floor in ≤7 seconds (without aids/orthoses),
* Able to complete the 6MWD test with a distance of at least 75m
* Receiving glucocorticoids for a minimum of 6 months immediately prior to screening, with no significant change in total daily dosage or dosing regimen for a minimum of 3 months immediately prior to screening and a reasonable expectation that total daily dosage and dosing regimen will not change significantly for the duration of the study
* QTc \<450msec
* On adequate contraception
* Able to comply with and complete all protocol requirements

Exclusion Criteria:

* any additional missing exon for DMD
* Current of history of liver or renal disease or impairment
* Acute illness within 4 weeks of the first dose
* Use of prohibited meds within 6 months of fist dose
* Current participation in any other investigational clinical trial
* Positive hepatitis B surface antigen, hepatitis C antibody test, or human immunodeficiency virus (HIV) test at screening
* Symptomatic cardiomyopathy
* Children in Care
B: Major Inclusion and Exclusion Criteria:

Inclusion Criteria:

A subject must meet all of the following criteria to be eligible for this study.

* Be a male with DMD and have an out-of-frame deletion(s) that may be corrected by skipping exon 51 \[e.g., deletions of exons 45-50, 47-50, 48-50, 49-50, 50, 52, 52-63\], as confirmed in a Clinical Laboratory Improvement Act-accredited laboratory by any of the peer-reviewed and published methodology that evaluates all exons (including, but not limited to, multiplex ligation-dependent probe, comparative genomic hybridization, and single condition amplification/internal primer analysis).
* Be between the ages of 7 and 13 years, inclusive.
* Have stable cardiac function and stable pulmonary function (forced vital capacity \[FVC\] ≥50% of predicted and not require supplemental oxygen) that, in the Investigator's opinion, is unlikely to decompensate over the duration of the study.
* Be receiving treatment with oral corticosteroids and have been on a stable dose for at least 24 weeks before study entry. Subjects may be allowed to take other (non-RNA antisense or gene therapy) medication (including angiotensin-converting enzyme \[ACE\] inhibitors, β blockers, losartan potassium, and coenzyme Q) as long as they have been on a stable dose of the medication for 24 weeks before the screening visit (Visit 1) and the dose will remain constant throughout the study.
* Have intact right and left biceps muscles or an alternative upper arm muscle group.
* Achieve an average distance within 200m and 400m ±10% (i.e. within 180m and 440m) while walking independently over six minutes.
* Have a left ventricular ejection fraction (LVEF) of \>40% based on the ECHO that is obtained at the screening visit (Visit 1). A subject who has abnormal ECHO findings but who has an LVEF of \>40% may be enrolled in the study at the Investigator's discretion; however, the subject must have been receiving stable doses of ACE inhibitors or β blockers for at least 24 weeks before study entry.
* Have a parent(s) or legal guardian(s) who is able to understand and comply with the all of the study procedure requirements.
* Be willing to provide informed assent and have a parent(s) or legal guardian(s) who is willing to provide written informed consent for the subject to participate in the study.

Exclusion Criteria:

A subject who meets any of the following criteria will be excluded from this study.

* Use of any pharmacologic treatment, other than corticosteroids, that might have an effect on muscle strength or function within 12 weeks before study entry (e.g., growth hormone, anabolic steroids).
* Previous treatment with the experimental agents eteplirsen, BMN-195, or PRO051.
* Previous treatment with any other experimental agents or participation in any other DMD interventional clinical study within 12 weeks before entry into this study; including use of the shock training system or "STS," or planned use during this study.
* Surgery within 3 months before study entry or planned surgery at any time during this study.
* Presence of other clinically significant illness at the time of study entry, including significant renal dysfunction (as measured by urinary cystatin C, KIM-1, or urinary total protein), or average heart rate during screening Holter monitoring in excess of 110 bpm (unless subsequently treated and confirmed controlled and stable on a β-blocker) or QTc \>450 ms.
* Use of any aminoglycoside antibiotic within 12 weeks before the screening visit (Visit 1) or need for use of an aminoglycoside antibiotic during the study (unless discussed and agreed with the Principal Investigator and medical monitor).
* Prior or ongoing medical condition that, in the Investigator's opinion, could adversely affect the safety of the subject or that makes it unlikely that the course of treatment or follow-up would be completed or could impair the assessment of study results.
C: Inclusion Criteria:

* DMD patients age 7 years and older (and able to complete cardiac MRI without sedation) with preserved left ventricular (LV) systolic function and abnormal heart muscle by late post-gadolinium imaging (LGE)

Exclusion Criteria:

* renal insufficiency (GFR \<40 mL/min/m2)
* non-MR compatible implants (e.g. neurostimulator, AICD)
* severe claustrophobia
* allergy to gadolinium contrast
* prior use of or known allergy to epleronone
* use of potassium-sparing diuretics
* serum potassium level of \>5.0 mmol/L
D: Inclusion Criteria:

* Duchenne muscular dystrophy patients of all ages
* Null mutation of the dystrophin gene or muscle with \<5% dystrophin
* Doppler echocardiogram with ejection fraction (EF) \<55% within 30 days of enrollment
* Ability to cooperate for testing
* Glucocorticoid treatment acceptable including daily or weekend administration of prednisone or deflazacort

Exclusion Criteria:

* Patients with EF 55% or greater
* Patients with EF \<40% after washout
* Patients taking \>5 mg lisinopril, or \>25 mg losartan or \>5 mg enalapril
* Skeletal deformities or pulmonary anatomical variants that preclude consistent measures of Doppler echocardiography

Answer: D