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

A Phase 1b/2a Trial of Dantrolene Sodium in Pediatric and Adult Patients With Wolfram Syndrome

Sponsors

Lead Sponsor: Washington University School of Medicine

Collaborator: National Institutes of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Source Washington University School of Medicine
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 6-month treatment period with an optional extension phase up to 24 months, 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.

Overall Status Recruiting
Start Date January 2017
Completion Date March 2021
Primary Completion Date December 2020
Phase Phase 1/Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Number of participants with treatment-related adverse events as assessed by liver function tests 6 months with an optional extension phase up to 24 months
Secondary Outcome
Measure Time Frame
Changes in C-peptide levels in participants assessed by the ELISA assay 6 months with an optional extension phase up to 24 months
Changes in Visual Functioning in participants assessed by Visual Functioning Questionnaire-25. 6 months with an optional extension phase up to 24 months
Changes in best-corrected visual acuity in participants measured by Snellen optotype 6 months with an optional extension phase up to 24 months
Changes in Neurological Functions in participants assessed by the Wolfram Unified Rating Scale (WURS) 6 months with an optional extension phase up to 24 months
Enrollment 50
Condition
Intervention

Intervention Type: Drug

Intervention Name: dantrolene sodium

Description: 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 6-month treatment period with an optional extension phase up to 24 months, 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.

Eligibility

Criteria:

Inclusion Criteria:

Patients must meet all of the following criteria to be eligible for enrolment:

1. The patient has a definitive diagnosis of Wolfram syndrome, as determined by the following:

a. Documented functionally relevant recessive mutations on both alleles of the WFS1 gene or dominant mutation on one allele of the WFS1 gene based on historical test results (if available) or from a qualified laboratory at screening.

2. The patient is at least 5 years of age (biological age) at the time of written informed consent.

3. The patient, patient's parent(s), or legally authorized guardian(s) must have voluntarily signed an Institutional Review Board/Independent Ethics Committee-approved informed consent form after all relevant aspects of the study have been explained and discussed with the patient. The guardians' consent and patient's assent, as relevant, must be obtained.

Exclusion Criteria:

Patients who meet any of the following criteria are not eligible for this study:

1. The patient has clinically significant non-Wolfram related CNS involvement which is judged by the investigator to be likely to interfere with the accurate administration and interpretation of protocol assessments.

2. The patient has a known defect in oxidative phosphorylation (such as a confirmed mitochondrial myopathy)

3. The patient has abnormal liver function (defined as serum transaminases more than twice the upper limit of normal for the reference laboratory)

4. The patient has a significant medical or psychiatric co-morbidity that might affect study data or confound the integrity of study results.

5. The patient has received treatment with any investigational drug within the 30 days prior to study entry.

6. The patient has received blood product transfusions within 90 days prior to screening.

7. The patient is unable to comply with the protocol, (e.g. has a clinically relevant medical condition making implementation of the protocol difficult, unstable social situation, known clinically significant psychiatric/behavioural instability, is unable to return for safety evaluations, or is otherwise unlikely to complete the study), as determined by the Investigator.

8. The patient has a known history of central apnea and/or ventilation requirements.

9. The patient has a known history of chronic obstructive pulmonary disease, pleural effusion, and/or myocardial disease.

Gender: All

Minimum Age: 5 Years

Maximum Age: 60 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Fumihiko Urano, MD Study Director Washington University School of Medicine
Overall Contact

Last Name: Stacy Hurst, RN, BSN

Phone: +1-314-747-3294

Email: [email protected]

Location
Facility: Status: Contact: Contact Backup: Investigator: Washington University School of Medicine Stacy Hurst, RN, BSN 314-747-3294 [email protected] Fumihiko Urano, MD Principal Investigator
Location Countries

United States

Verification Date

May 2020

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Pediatric

Type: Experimental

Description: Pediatric patients treated with dantrolene sodium

Label: Adult

Type: Experimental

Description: Adult patients treated with dantrolene sodium

Patient Data Yes
Study Design Info

Allocation: Non-Randomized

Intervention Model: Single Group Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov