Tracking Neurodegeneration in Early Wolfram Syndrome

NCT02455414 | Completed

• 2 other identifiers: 201301004R01HD070855-02
• Study Type: observational
• Target: 101
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to determine the pattern of early neurodegenerative changes in WFS (Wolfram Syndrome). The investigator will perform cross-sectional and longitudinal assessments of youth with WFS, targeting sensitive neural systems with quantified neuroimaging and behavioral measures. In addition, the investigator will establish the utility of a WFS severity rating scale (WFS Unified Rating Scale or WURS). Preliminary data support the feasibility of this approach and its potential to generate important new information about neurodevelopmental and neurodegenerative patterns in WFS. This work is necessary to position the field for future clinical trials to test interventions for WFS neurodegeneration. Ultimately, a better understanding of the trajectory of neurodegeneration in WFS and the development of effective interventions may be relevant to other more common neurodegenerative and endocrine (Type 1 and Type 2 diabetes) diseases in which ER stress has been implicated.

Conditions

Type 1 Diabetes; Diabetes Insipidus; Diabetes Mellitus; Wolfram Syndrome

Outcome Measures

Primary Outcomes (1)

• Change in regional brain volume

  MRI measures of regional brain volumes over time

  annually for 5 years

Secondary Outcomes (1)

• Change in disease severity score

  annually for 5 years

Study Arms (6)

Wolfram Syndrome Group

* Participant has confirmation of a WFS1 mutation OR * Both of the following conditions: diabetes mellitus requiring insulin and optic nerve atrophy diagnosed by a physician. Both conditions diabetes mellitus and optic nerve atrophy had to be diagnosed at age younger than 18 years old

WFS Pre-symptomatic Sibling Group

* Has had genotyping * Willingness to share result of genotyping * Participant has confirmation of WFS1 (+/+) mutation but is asymptomatic.

WFS Control Sibling Group

* Has had genotyping * Willingness to share result of genotyping * Patient has confirmation of NO WFS1 mutation (-/-) or confirmation as a carrier (+/- or -/+).

T1DM Group

* Age within the 0-28 yrs age range of WS participant * Dx of T1 diabetes mellitus

Healthy Control (HC) Group

• Age within the 0-28 yrs age range of WFS participants

Proxy Group

Adult Biological parent(s), biological caregiver or non-biological caregiver of adult and minor participants in the any of the groups.

Eligibility Criteria

• Age: 1 Day+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Age, gender and handedness matched participants between the age of 1 day to no upper limit.

You may qualify if:

• Participant has confirmation of a WFS1 mutation OR
• Both of the following conditions: diabetes mellitus requiring insulin and optic nerve atrophy diagnosed by a physician. Both conditions diabetes mellitus and optic nerve atrophy had to be diagnosed at age younger than 18 years old

You may not qualify if:

• Participant is unaware of their diagnosis.
• Inability of patient or guardian to understand informed consent.
• Advanced disease that makes traveling too problematic and/or uncomfortable for the patient and/or guardian, such as use of ventilator or inability to walk.
• T1DM Group:
• Age within the 0-28 yrs age range of WS participant
• Dx of T1 diabetes mellitus
• Participant is unaware of their diagnosis.
• Inability of patient or guardian to understand informed consent.
• Diagnosis of any major neurological or medical condition.
• Chronic disease other than T1DM, well-controlled asthma, or Hashimoto's thyroiditis.
• Other current serious medical illness
• Co-morbid psychiatric illness: such as mania, mental retardation, or psychoactive drug dependence.
• Co-morbid neurological illness: stroke, seizure, major loss of consciousness, other brain trauma/surgery, or head injuries (i.e. near drowning), encephalitis, or hydrocephalus, blindness, deafness.
• Pre-maturity at birth \>4 wks early (\<36 wk term) w/ sequelae (e.g. on respirator at NICU)
• Contraindication to MRI scan (e.g. claustrophobia, metal implants, foreign bodies)

Sponsors & Collaborators

• Washington University School of Medicine: lead
• National Institutes of Health (NIH): collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (1)

• Bischoff AN, Reiersen AM, Buttlaire A, Al-Lozi A, Doty T, Marshall BA, Hershey T; Washington University Wolfram Syndrome Research Group. Selective cognitive and psychiatric manifestations in Wolfram Syndrome. Orphanet J Rare Dis. 2015 May 30;10:66. doi: 10.1186/s13023-015-0282-1.

  PMID: 26025012 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

A skin biopsy will be obtained from which the investigator will sequence all the exons and exon-intron junctions of the WFS1 gene. In some cases, the investigator will also sequence other genes related to Wolfram syndrome including WFS2, MANF, and Caspase-12. If the investigator doesn't find mutations in these genes, a whole-exome sequencing may be performed. The genetic test provided has the potential to create a uniquely-identifiable fingerprint that could possibly identify a participant.

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetes Insipidus; Diabetes Mellitus; Wolfram Syndrome

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Pituitary Diseases; Deaf-Blind Disorders; Deafness; Hearing Loss; Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Optic Atrophies, Hereditary; Optic Atrophy; 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; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Study Officials

• Tamara Hershey, PhD

  Washington University Medical School

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2015
• First Posted: May 27, 2015
• Study Start: April 1, 2012
• Primary Completion: July 12, 2017
• Study Completion: July 12, 2017
• Last Updated: July 11, 2018

Record last verified: 2018-07

Locations

US (1)