Wolfram Syndrome and WFS1-related Disorders International Registry and Clinical Study

NCT02841553 | Recruiting

• 2 other identifiers: 201107067R01DK132090
• Study Type: observational
• Target: 5,000
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetes Mellitus; Optic Nerve Atrophy; Deafness; Diabetes Insipidus; Ataxia; Wolfram Syndrome

Keywords

Endoplasmic Reticulum Stress

Outcome Measures

Primary Outcomes (1)

• Changes in C-peptide levels in participants

  The investigators will monitor base-line C-peptide levels in participants' blood.

  10 years

Secondary Outcomes (1)

• Changes in best-corrected visual acuity in participants measured by Snellen optotype

  10 years

Eligibility Criteria

• Age: 0 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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)
• loss of function mutation in WFS1/CISD2 AND/OR family history of Wolfram syndrome
• Minimum Required
• major OR
• major plus 2 minor criteria OR
• pathological WFS1 or CISD2 mutations are identified

You may not qualify if:

• Inability of a patient and/or a guardian to obtain help with translation and thus, inability to understand questionnaire.
• Parent, Sibs, and Spouses:

Sponsors & Collaborators

• American Diabetes Association: collaborator
• National Institutes of Health (NIH): collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Related Publications (1)

• Urano F. Wolfram Syndrome: Diagnosis, Management, and Treatment. Curr Diab Rep. 2016 Jan;16(1):6. doi: 10.1007/s11892-015-0702-6.

  PMID: 26742931 RESULT

Related Links

• Wolfram Syndrome International Registry and Clinical Study

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.

MeSH Terms

Conditions

Wolfram Syndrome; Diabetes Mellitus; Optic Atrophy; Deafness; Diabetes Insipidus; Ataxia

Condition Hierarchy (Ancestors)

Deaf-Blind Disorders; Hearing Loss; Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Optic Atrophies, Hereditary; Optic Nerve Diseases; Cranial Nerve Diseases; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Sensation Disorders; Neurologic Manifestations; Blindness; Vision Disorders; Eye Diseases, Hereditary; Eye Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Diabetes Mellitus, Type 1; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Pituitary Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Dyskinesias

Central Study Contacts

Fumihiko Urano, MD

CONTACT

(314) 477-1527; wolframsyndrome@wustl.edu

Ashley Raterman, RN

CONTACT

(314) 477-1527; araterman@wustl.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Target Duration: 20 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2016
• First Posted: July 22, 2016
• Study Start: July 1, 2011
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: December 23, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

US (1)