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

Brief Title

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

Official Title

A Phase 1b/2a Trial of Dantrolene 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 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.

Study Phase

Phase 1/Phase 2

Study Type


Primary Outcome

Number of participants with treatment-related adverse events as assessed by liver function tests

Secondary Outcome

 Changes in C-peptide levels in participants assessed by the ELISA assay


Wolfram Syndrome


dantrolene sodium

Study Arms / Comparison Groups

Description:  Pediatric patients treated with dantrolene sodium


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

January 2017

Completion Date

February 2023

Primary Completion Date

February 2023

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

             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.




5 Years - 60 Years

Accepts Healthy Volunteers



Fumihiko Urano, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID


Secondary IDs


Responsible Party


Study Sponsor

Washington University School of Medicine


 National Institutes of Health (NIH)

Study Sponsor

Fumihiko Urano, MD, Study Director, Washington University School of Medicine

Verification Date

February 2022