A multicenter, open-label, single-arm study of a TRPV2 inhibitor against cardiomyopathy of muscular dystrophy

• Register: JPRN
• Last refreshed on: 17 October 2023
• Main ID: JPRN-UMIN000031965
• Date of registration: 30/03/2018
• Prospective Registration: Yes
• Primary sponsor: National Hospital Organization Toneyama National Hospital
• Public title: A multicenter, open-label, single-arm study of a TRPV2 inhibitor against cardiomyopathy of muscular dystrophy
• Scientific title: A multicenter, open-label, single-arm study of a TRPV2 inhibitor against cardiomyopathy of muscular dystrophy - Tranilast-MD
• Date of first enrolment: 2018/12/14
• Target sample size: 20
• Recruitment status: Complete: follow-up continuing
• URL: https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000036486
• Study type: Interventional
• Study design: Single arm Non-randomized
• Phase: Not selected

Countries of recruitment

Japan

Contacts

• Name: Yutaka Ito
• Affiliation: National Hospital Organization Nagoya Medical Center Clinical Research Center

• Name: Tsuyoshi Matsumura
• Affiliation: National Hospital Organization Toneyama National Hospital Neurology

Key inclusion & exclusion criteria

Inclusion criteria:
Exclusion criteria: 1) Acute stage heart failure condition (using cardiotonic, diuretic, antiarrhythmic drug intravenously) 2) From 2 weeks before the start of administration to the start of administration Directions of digitalis, diuretic, aldosterone antagonist, cardiotonic agent, antiarrhythmic drug are not fixed 3) With a lethal arrhythmia including ventricular premature contraction of more than four (short run)), excluding those with transplanted implantable defibrillators 4) With serious renal dysfunction (estimated glomerular filtration ratio (eGFR) using cystatin C of less than 30 mL/min/1.73 m2) Male: eGFR = (104 ^ Cystatin C-1.019^ 0.996age (years)) - 8 Female: eGFR = (104 ^ Cystatin C-1.019 ^ 0.996age (years) ^ 0.929) - 8 For those aged 18 or less, cyctain C of 2.5 mg/L or more is used. 5) With severe liver function disorder (T. Bil of 10 mg/dl or more, AST and ALT of 500 IU/L or more, ALP of 5 times or more of the normal upper limit, PT of 40% or less, bleeding tendency, hepatic failure symptoms (fulminant hepatitis), cirrhosis of the liver, liver tumor, jaundice prolonged for more than 6 months) (equivalent to grade 3 in "Classification criteria for severity of adverse drug reactions" ) 6) Marked white blood cell (WBC) decrease (less than 3000/mm^3), platelet (Plt) decrease (less than 80,000/mm^3) 7) Having a history of hypersensitivity to tranilast 8) Pregnant or possibly pregnant 9) For whom the principal investigator/sub-investigators judged not appropriate for participation in this study

Age minimum: 13years-old
Age maximum: Not applicable
Gender: Male and Female

Health Condition(s) or Problem(s) studied

Heart failure patients with muscular dystrophy who showed brain natriuretic peptide (BNP) of 100 pg/mL or more in spite of myocardial protection treatment

Intervention(s)

Tranilast 300 mg/day is administered three times per day as the study treatment. The start date of study treatment is defined as the medication start date, and 28 weeks of study treatment will be performed (in principle, by outpatient administration). We reconfirm consent for continuation of administration at 28 weeks, and if consent is obtained, further treatment for 116 weeks will be carried out. As long as there are no particular problems, the outpatient visit during the observation period is in 4 weeks (21-35 days), 12 weeks (77-91 days), 20 weeks (134-147 days), 24 weeks (161-175 days), and 28 weeks (190-203 days) after starting medication. A prescription until the next outpatient visit will be issued at the consultation. The outpatient visit after consent reconfirmation is done at 12-weeks intervals after 36 weeks, and the prescription until the next outpatient visit will be issued until the next 144 weeks after starting medication at the consultation. Evaluation of various examination findings including clinical findings, cardiac functions, respiratory functions, motor function, QOL Questionnaire (MDQoL-60, SF-12), and adverse events at the designated timing. In order to confirm TRPV2 inhibitory effect by tranilast and to assess its effectiveness as a biomarker, central laboratory tests for the TRPV2 expression analysis will be performed.

Primary Outcome(s)

The change in BNP before the start of administration (using the average of values in the pre-treatment observation period and at the start of administration) to 24 weeks (using the average of values at 20 weeks, 24 weeks and 28 weeks)

Secondary Outcome(s)

1) Cardiac events (change of oral medicine for cardiac failure due to cardiac function exacerbation (ACEI/ARB, Beta blocker, digitalis, diuretic, aldosterone antagonist, cardiotonic agent or antiarrhythmic agent), administration of intravenous drugs (cardiotonic agents, diuretics or antiarrhythmic agent), hospitalization due to heart failure or prolongation of hospitalization) 2) All deaths 3) Left ventricula fractional shortening (FS) 4) Human atrial natriuretic peptide (hANP), cardiac troponin T (cTnT) 5) The expression of transient receptor potential cation channel, subfamily V, member 2 (TRPV2) expression on cytoplasminc membrane of isolated peripheral blood mononuclear cells (PBMCs) 6) Hand finger muscle strength (pinch strength), creatine kinase (CK) 7) Muscular dystrophy quality of life-60 (MDQOL-60), The short form (12) health survey (SF-12) 8) Adverse events

Source(s) of Monetary Support

National Hospital Organization

Ethics review

Status: YES
Approval date: 23/10/2019
Contact:

Results

• Results available: Yes
• Date Completed: 31/03/2023