Clinical Trial: A Clinical Trial of Dantrolene Sodium in Pediatric and Adult Patients With Wolfram Syndrome

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase 1b Safety Trial of Dantronele Sodium in Pediatric and Adult Patients With Wolfram Syndrome

Brief Summary:

Wolfram syndrome is a rare genetic disorder characterized by juvenile-onset diabetes mellitus, diabetes insipidus, optic nerve atrophy, hearing loss, and neurodegeneration. The purpose of this study is to assess the safety and tolerability of dantrolene sodium in patients with Wolfram syndrome. In addition, we will assess the efficacy of dantrolene sodium on the cardinal manifestations of Wolfram syndrome, including visual acuity, remaining beta cell functions, and neurological functions.

There is a screening period up to 56 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.

Detailed Summary:
Sponsor: Washington University School of Medicine

Current Primary Outcome: Number of participants with treatment-related adverse events as assessed by liver function tests [ Time Frame: 6 months ]

Original Primary Outcome: Number of participants with treatment-related adverse events as assessed by liver function tests [ Time Frame: 6 months ]

Current Secondary Outcome:

• Changes in C-peptide levels in participants assessed by the ELISA assay [ Time Frame: 6 months ]
  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 ]
  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 ]
  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 ]
  Neurological functions will be assessed by the Wolfram Unified Rating Scale (WURS) and standard neurological assessments.

Original Secondary Outcome:

• Changes in C-peptide levels in participants assessed by the ELISA assay [ Time Frame: 6 months ]
  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 dynamic balance in participants assessed by the Mini-Balance Evaluation Systems Test (Mini BESTest) [ Time Frame: 6 months ]
  Balance will be measured by the Mini-Balance Evaluation Systems Test (Mini BESTest). The Mini BESTest is a clinician rated assessment of dynamic balance. Lower scores are indicative of impairments in balance. The total possible score on this evaluation is 28, indicating no balance impairmen
• Changes in best-corrected visual acuity in participants measured by Snellen optotype [ Time Frame: 6 months ]
  Best-corrected visual acuity will be measured by Snellen optotype. Higher logMar scores indicate worse vision)

Dates:
Date Received: July 6, 2016
Date Started: January 2017
Date Completion: March 2019
Last Updated: March 24, 2017
Last Verified: March 2017