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Wolfram Syndrome International Registry and Clinical Study

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ClinicalTrials.gov Identifier: NCT02841553
Recruitment Status : Recruiting
First Posted : July 22, 2016
Last Update Posted : February 6, 2019
Sponsor:
Collaborators:
American Diabetes Association
National Institutes of Health (NIH)
Information provided by (Responsible Party):
Washington University School of Medicine

Brief Summary:

In this study, the investigators hypothesize that studying monogenic variants with strong effect associated with severe insulin deficiency of Wolfram syndrome will provide important insights into the more complex type 1 and type 2 diabetes mellitus.

Aim 1. Establish and maintain a registry of patients with Wolfram syndrome. An Internet based registry will be employed to enroll participants with the clinical diagnosis of Wolfram syndrome (insulin dependent DM and bilateral OA). Clinical information regarding age of diagnosis and progression of the disease will be collated and analyzed to better define its natural history, along with potential metabolic phenotypes such as glucose intolerance of heterozygous parents and unaffected sibs.

If not already completed, blood for WFS1 sequence analysis will be obtained on the participants (parents and sibs also for control purposes) and sent to a CLIA certified lab to define the mutation. This information will benefit patient families and referring physicians by providing a genetic diagnosis and where indicated. The Wolfram Syndrome Registry will foster international collaborations to more efficiently and systematically collect Wolfram syndrome patients and their clinical and experimental data.


Condition or disease
Wolfram Syndrome Diabetes Mellitus Optic Nerve Atrophy Deafness Diabetes Insipidus Ataxia

  Show Detailed Description

Study Type : Observational [Patient Registry]
Estimated Enrollment : 200 participants
Observational Model: Cohort
Time Perspective: Cross-Sectional
Target Follow-Up Duration: 20 Years
Official Title: Wolfram Syndrome International Registry and Clinical Study
Study Start Date : July 2011
Estimated Primary Completion Date : December 2025
Estimated Study Completion Date : December 2025





Primary Outcome Measures :
  1. Changes in C-peptide levels in participants [ Time Frame: 10 years ]
    The investigators will monitor base-line C-peptide levels in participants' blood.


Secondary Outcome Measures :
  1. Changes in best-corrected visual acuity in participants measured by Snellen optotype [ Time Frame: 10 years ]
    Best-corrected visual acuity will be measured by Snellen optotype. Higher logMar scores indicate worse vision


Biospecimen Retention:   Samples With DNA
DNA samples will be used to sequence the WFS1 gene. If no mutations are found in this gene and the subject's doctor(s) are convinced he has Wolfram Syndrome, investigators may also offer sequencing of the WFS2 (CISD2) gene or of autosomal dominant hearing loss genes.


Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Any patient worldwide with a clinical diagnosis of Wolfram syndrome and with access to the Internet can be enrolled in the Registry. Since the disease usually manifests in the first decade of life and tends to have an inevitably progressive course, participation of minors is important for establishing the natural course of the disease.
Criteria

Any patient worldwide with a diagnosis of Wolfram syndrome and with access to the Internet can be enrolled in the Registry. Since the disease usually manifests in the first decade of life and tends to have an inevitably progressive course, participation of minors is important for establishing the natural course of the disease.

Inclusion Criteria:

Major Criteria

  • Diabetes mellitus <16 yrs
  • Optic atrophy <16 yrs

Minor Criteria

  • Diabetes insipidus
  • Diabetes mellitus >16yrs
  • Optic atrophy >16 yrs
  • Sensorineural deafness
  • Neurological signs (ataxia, epilepsy, cognitive impairment)
  • Renal tract abnormalities (structural or functional)
  • 1 loss of function mutation in WFS1/CISD2 AND/OR family history of Wolfram syndrome

Minimum Required

  • 2 major OR
  • 1 major plus 2 minor criteria OR
  • 2 pathological WFS1 or CISD2 mutations are identified

Other variable suggestive evidence

  • Hypogonadism (males)
  • An absence of type 1 diabetes auto-antibodies
  • Bilateral cataracts
  • Psychiatric disorder
  • Gastrointestinal

Exclusion Criteria:

Inability of a patient and/or a guardian to obtain help with translation and thus, inability to understand questionnaire.

Parent, Sibs, and Spouses:

- Parents, sibs, and spouses that are unaffected will be recruited as controls. Inclusion criterion is having the unaffected status and exclusion criterion is if the person cannot understand the Informed Consent Document.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02841553


Contacts
Contact: Fumihiko Urano, MD +1-314-362-8683 urano@wustl.edu

Locations
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Fumihiko Urano, MD    314-362-8683    urano@wustl.edu   
Contact: Cris Brown, BS    +1-314-362-8684      
Principal Investigator: Fumihiko Urano, MD         
Sponsors and Collaborators
Washington University School of Medicine
American Diabetes Association
National Institutes of Health (NIH)

Additional Information:
Publications of Results:
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT02841553     History of Changes
Other Study ID Numbers: 201107067
UL1TR000448 ( U.S. NIH Grant/Contract )
First Posted: July 22, 2016    Key Record Dates
Last Update Posted: February 6, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Publications and through the NCATS GRDR Program.

Keywords provided by Washington University School of Medicine:
Endoplasmic Reticulum Stress

Additional relevant MeSH terms:
Deafness
Hearing Loss
Diabetes Mellitus
Syndrome
Atrophy
Diabetes Insipidus
Wolfram Syndrome
Optic Atrophy
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Disease
Pathologic Processes
Pathological Conditions, Anatomical
Hearing Disorders
Ear Diseases
Otorhinolaryngologic Diseases
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Kidney Diseases
Urologic Diseases
Pituitary Diseases
Deaf-Blind Disorders
Optic Atrophies, Hereditary
Optic Nerve Diseases
Cranial Nerve Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases