A Phase 1/2 interventional study of dantrolene sodium in Wolfram Syndrome, Diabetes Mellitus and Optic Nerve Atrophy, sponsored by Washington University School of Medicine. Completed at 1 site in United States. Open to participants aged 5 Years to 60 Years. Per ClinicalTrials.gov, last updated 2024-03-13.
Sponsored by Washington University School of Medicine · Phase 1/2, Interventional, and Treatment
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.
The Primary Objective of this study is:
To 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 with an optional extension phase up to 24 months. Patients who express the wish to continue in the optional extension phase on dantrolene sodium will be offered this possibility.
The Secondary Objectives of this study are:
8,290 studies on the registry are indexed under Diabetes Mellitus; 1,077 are open to participants now.
This study's enrollment of 21 is below the median of 80 across 6,023 interventional studies indexed under Diabetes Mellitus.
Browse Diabetes Mellitus studies →Washington University School of Medicine is the lead sponsor of 1,803 studies on the registry; 271 are open to participants now.
Of its 329 completed or terminated interventional studies of FDA-regulated products, 216 (66%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Patients must meet all of the following criteria to be eligible for enrolment:
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.
Exclusion Criteria:
Patients who meet any of the following criteria are not eligible for this study:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
COPD
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Pediatric patients treated with dantrolene sodium
Drug: dantrolene sodium
Adult patients treated with dantrolene sodium
Drug: dantrolene sodium
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.
Also known as: dantrolene
Number of Participants With Treatment-related Adverse Events as Assessed by Liver Function Tests
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.
Time frame: 6 months
Changes in C-peptide Levels in Participants Assessed by the ELISA Assay
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.
Time frame: 6 months
Changes in Visual Functioning in Participants Assessed by Visual Functioning Questionnaire-25.
Changes in Visual Functioning in participants assessed by Visual Functioning Questionnaire-25. The Visual Functioning Questionnaire-25 (VFQ-25) is divided into several subdomains, each assessing a specific aspect of visual functioning and its impact on an individual's life. There are a total of 11 subdomains in the VFQ-25. To calculate the total score on the VFQ-25, we follow these steps: 1. Calculate Subdomain Scores, 2. Weighted Sum 3. Calculate Total Score VFQ-25 provides scores that range from 0 to 100. The total score represents the overall impact of visual functioning on the individual's quality of life, with higher scores indicating better quality of life and less impact from vision problems.
Time frame: 6 months
Changes in Best-corrected Visual Acuity in Participants Measured by LogMar Score
Best-corrected visual acuity is assessed using the Snellen optotype and then converted into LogMar Scores (Minimum: -0.30, Maximum: 3.0). A higher LogMar score signifies poorer vision.
Time frame: 6 months
Changes in Neurological Functions in Participants Assessed by the Wolfram Unified Rating Scale (WURS)
Neurological functions are assessed by the Wolfram Unified Rating Scale (WURS). The WURS is divided into the following subscales: Physical Assessment and Behavioral Assessment. Physical Assessment (34 items rated on a scale from 0 = no symptoms to 4 = highest severity, minimum: 0, Maximum: 136) and Behavioral Assessment (9 items rated on frequency and severity from 0 = normal behavior to 3 = highest severity, Minimum: 0, Maximum: 27). Subscale scores are summed to calculate the total scores (minimum: 0, Maximum: 163). Higher total scores indicate more severe neurological manifestations.
Time frame: 6 months
| Milestone | Pediatric | Adult |
|---|---|---|
| Started | 8 | 13 |
| Completed | 8 | 11 |
| Not completed | 0 | 2 |
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.
| Participants | Pediatric | Adult |
|---|---|---|
| Baseline | 0 | 0 |
| 6 months | 0 | 2 |
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.
| ng/mL | Pediatric | Adult |
|---|---|---|
| Baseline | 0.34 ± 0.07 | 0.19 ± 0.05 |
| 6 months | 0.47 ± 0.13 | 0.30 ± 0.09 |
Changes in Visual Functioning in participants assessed by Visual Functioning Questionnaire-25. The Visual Functioning Questionnaire-25 (VFQ-25) is divided into several subdomains, each assessing a specific aspect of visual functioning and its impact on an individual's life. There are a total of 11 subdomains in the VFQ-25. To calculate the total score on the VFQ-25, we follow these steps: 1. Calculate Subdomain Scores, 2. Weighted Sum 3. Calculate Total Score VFQ-25 provides scores that range from 0 to 100. The total score represents the overall impact of visual functioning on the individual's quality of life, with higher scores indicating better quality of life and less impact from vision problems.
| units on a scale | Pediatric | Adult |
|---|---|---|
| Baseline | 68 ± 2.3 | 74.3 ± 1.3 |
| 6 months | 70.5 ± 2.9 | 73.5 ± 2.4 |
Best-corrected visual acuity is assessed using the Snellen optotype and then converted into LogMar Scores (Minimum: -0.30, Maximum: 3.0). A higher LogMar score signifies poorer vision.
| LogMAR | Pediatric | Adult |
|---|---|---|
| Baseline | 0.6 ± 0.2 | 0.8 ± 0.2 |
| 6 months | 0.6 ± 0.2 | 0.9 ± 0.2 |
Neurological functions are assessed by the Wolfram Unified Rating Scale (WURS). The WURS is divided into the following subscales: Physical Assessment and Behavioral Assessment. Physical Assessment (34 items rated on a scale from 0 = no symptoms to 4 = highest severity, minimum: 0, Maximum: 136) and Behavioral Assessment (9 items rated on frequency and severity from 0 = normal behavior to 3 = highest severity, Minimum: 0, Maximum: 27). Subscale scores are summed to calculate the total scores (minimum: 0, Maximum: 163). Higher total scores indicate more severe neurological manifestations.
| score on a scale | Pediatric | Adult |
|---|---|---|
| Baseline | 21.3 ± 6.4 | 20.5 ± 2.8 |
| 6 months | 18.4 ± 5.7 | 18.6 ± 4.5 |
Collected over 6 months. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Pediatric | 0/8 (0%) | 0/8 (0%) | 8/8 (100%) |
| Adult | 0/11 (0%) | 0/11 (0%) | 11/11 (100%) |
| Event | Pediatric | Adult |
|---|---|---|
| FatigueNervous system disorders | 3/8 | 5/11 |
| WeaknessNervous system disorders | 3/8 | 1/11 |
| Hypoglycemia (mild)Endocrine disorders | 3/8 | 4/11 |
| HeadachesNervous system disorders | 2/8 | 4/11 |
| DiarrheaGastrointestinal disorders | 2/8 | 3/11 |
| hyponatremiaRenal and urinary disorders | 1/8 | 3/11 |
| Urinary Tract InfectionRenal and urinary disorders | 1/8 | 3/11 |
| DizzinessNervous system disorders | 2/8 | 1/11 |
| HyperglycemiaEndocrine disorders | 2/8 | 1/11 |
| Elevated Hepatic enzymesHepatobiliary disorders | 0/8 | 2/11 |
| Age, Categorical(Participants) | Pediatric | Adult | Total |
|---|---|---|---|
| <=18 years | 8 | 0 | 8 |
| Between 18 and 65 years | 0 | 11 | 11 |
| >=65 years | 0 | 0 | 0 |
| Age, Continuous(years) | Pediatric | Adult | Total |
|---|---|---|---|
| Median | 13 (6 to 17) | 23 (18 to 32) | 18 (6 to 32) |
| Sex: Female, Male(Participants) | Pediatric | Adult | Total |
|---|---|---|---|
| Female | 6 | 8 | 14 |
| Male | 2 | 3 | 5 |
| Race (NIH/OMB)(Participants) | Pediatric | Adult | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 |
| White | 7 | 9 | 16 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 1 | 2 | 3 |
| Region of Enrollment(participants) | Pediatric | Adult | Total |
|---|---|---|---|
| United States | 8 | 11 | 19 |
| Abnormal liver function test results(Participants) | Pediatric | Adult | Total |
|---|---|---|---|
| Count of participants | 0 | 0 | 0 |
| C-peptide levels in participants during the oral mixed meal tolerance test(ng/mL) | Pediatric | Adult | Total |
|---|---|---|---|
| Mean | 0.34 ± 0.07 | 0.19 ± 0.05 | 0.25 ± 0.04 |
| Visual Functioning in participants assessed by Visual Functioning Questionnaire-25(units on a scale) | Pediatric | Adult | Total |
|---|---|---|---|
| Mean | 68 ± 2.3 | 74.3 ± 1.3 | 68.8 ± 3.1 |
2 further baseline measures are reported on the registry.
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No — We publish aggregated data in a scientific journal.
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Studies of the drug tested here: Dantrolene
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