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Title of study
A Clinical Trial of Dantrolene Sodium in Pediatric and Adult Patients With Wolfram Syndrome
Purpose of study
The purpose of this study is to assess the safety and tolerability of dantrolene sodium in patients with Wolfram syndrome. Wolfram syndrome is a rare genetic disorder, causing diabetes mellitus, optic atrophy, and deafness as well as various other possible disorders including premature death in most patients.
There is a screening period up to 28 days, a 24-week treatment period, and a 4-week safety follow-up period. Study assessments include medical & medication history, physical exams, neurological exams, eye exams, endocrine exams, vital signs, height, weight, electrocardiograms, blood and urine tests, pregnancy test if applicable, and questionnaires.
Ages 5 Years to 60 Years (Child, Adult)
Accepts healthy volunteers No
Primary outcome measures
Number of participants with treatment-related adverse events as assessed by liver function tests
[ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
The investigators assess the safety and tolerability of dantrolene sodium administered orally at upper end of therapeutic dose range for 6 months in patients with Wolfram syndrome. More specifically, the investigators perform liver function tests to check the levels of certain enzymes and proteins in participants’ blood. Levels that are higher or lower than normal can indicate liver problems. The liver function tests include: Alanine transaminase (ALT), Aspartate transaminase (AST), Alkaline Phosphatase (AP), and bilirubin.
Secondary outcome measures
Changes in C-peptide levels in participants assessed by the ELISA assay [ Time Frame: 6 months ] [ Designated as safety issue: No ]
The investigators determine the effect of dantrolene sodium on residual beta cell functions. The investigators monitor base-line C-peptide levels in participants’ blood. The investigators also monitor C-peptide levels in participant’s blood during the oral mixed meal tolerance test. The night before the oral mixed meal tolerance test, the participants will turn their insulin pump basal rate to 50% of the normal rate at midnight or take half of their evening dose of Lantus insulin and fasted from midnight until the test at 8 a.m. The mixed meal consists of 6 ml/kg (maximum 360 ml) of Boost Original (Société des Produits Nestlé S.A., Vevey, Switzerland). Blood for glucose and C-peptide measurement will be drawn at time 0 (fasting) and 30 minutes after the Boost. If a subject’s fasting glucose exceeds 11.1 mmol/l, the test will not be performed, but fasting glucose and C-peptide will be obtained.
Changes in Visual Functioning in participants assessed by Visual Functioning Questionnaire-25.
[ Time Frame: 6 months ] [ Designated as safety issue: No ]
Visual functions will be assessed by Visual Functioning Questionnaire – 25.
Changes in best-corrected visual acuity in participants measured by Snellen optotype [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Best-corrected visual acuity will be measured by Snellen optotype. Higher logMar scores indicate worse vision.
Changes in Neurological Functions in participants assessed by the Wolfram Unified Rating Scale (WURS) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Neurological functions will be assessed by the Wolfram Unified Rating Scale (WURS) and standard neurological assessments.
Fumihiko Urano, MD 1+314-362-8683 firstname.lastname@example.org
Teresa Arb, BSN, RN, CCRC 1+314-747-1217 email@example.com
Ashley N. Simpson, RN, BSN, CPN 1+314-286-1550 firstname.lastname@example.org