We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

Tracking Neurodegeneration in Early Wolfram Syndrome (TRACK)

This study is currently recruiting participants.
Verified October 2016 by Washington University School of Medicine
Sponsor:
ClinicalTrials.gov Identifier:
NCT02455414
First Posted: May 27, 2015
Last Update Posted: November 2, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
National Institutes of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Washington University School of Medicine
  Purpose
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.

Condition
Type 1 Diabetes Diabetes Insipidus Diabetes Mellitus Wolfram Syndrome

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Tracking Neurodegeneration in Early Wolfram Syndrome

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Change in regional brain volume [ Time Frame: annually for 5 years ]
    MRI measures of regional brain volumes over time


Secondary Outcome Measures:
  • Change in disease severity score [ Time Frame: annually for 5 years ]
    WURS physical severity score over time


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.

Estimated Enrollment: 150
Study Start Date: April 2012
Estimated Study Completion Date: April 2017
Estimated Primary Completion Date: April 2017 (Final data collection date for primary outcome measure)
Groups/Cohorts
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.

  Show Detailed Description

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Age, gender and handedness matched participants between the age of 1 day to no upper limit.
Criteria

Wolfram Syndrome Group (WFS):

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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:

Inclusion criteria:

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

Exclusion criteria:

  • 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)
  • Orthodontic braces. Full and top braces will exclude.

Healthy Control (HC) Group:

Inclusion criteria:

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

Exclusion criteria:

  • Inability of patient or guardian to understand informed consent.
  • Dx of T1 diabetes mellitus
  • Diagnosis of any major neurological or medical condition.
  • Chronic disease other than 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)
  • Orthodontic braces. Full and top braces will exclude. Bottom braces are ok (but the scan might not work out). Retainers are ok.

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

Inclusion criteria:

• Biological or non-biological parent/caregiver (proxy) of a participant.

Exclusion criteria:

• Proxy is unaware of the participant's diagnosis (as it applies).

  Contacts and Locations
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): NCT02455414


Contacts
Contact: Samantha Ranck, MSW 314-362-6514 rancks@npg.wustl.edu
Contact: Tasha Doty, MA 314-362-7160 dotyt@npg.wustl.edu

Locations
United States, Missouri
Washington University School of Medicine Recruiting
St. Louis, Missouri, United States, 63110
Contact: Samantha Ranck, MSW    314-362-6514    rancks@npg.wustl.edu   
Principal Investigator: Tamara G Hershey, PhD         
Sponsors and Collaborators
Washington University School of Medicine
National Institutes of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
Principal Investigator: Tamara Hershey, PhD Washington University Medical School
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT02455414     History of Changes
Other Study ID Numbers: 201301004
R01HD070855-02 ( U.S. NIH Grant/Contract )
First Submitted: March 5, 2015
First Posted: May 27, 2015
Last Update Posted: November 2, 2016
Last Verified: October 2016

Additional relevant MeSH terms:
Diabetes Mellitus
Syndrome
Diabetes Mellitus, Type 1
Nerve Degeneration
Diabetes Insipidus
Wolfram Syndrome
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Disease
Pathologic Processes
Autoimmune Diseases
Immune System Diseases
Kidney Diseases
Urologic 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