Wolfram SyndromeI-TRACKNCT03951298
I-Tracking Neurodegeneration in Early Wolfram Syndrome
An observational study of Wolfram Syndrome, run by Washington University School of Medicine at 1 site in United States.
Trial summary
Wolfram syndrome (WFS; OMIM #222300) is a rare autosomal recessive disease clinically defined in 1938 as the combination of childhood-onset insulin dependent diabetes, optic nerve atrophy, diabetes insipidus and deafness. Read more about this study
- Who is it for?
- Ages 1 day and older
- Conditions the study is for
- Wolfram Syndrome
- How many people
- 128 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Aug 2018to 31 Dec 2023
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 day and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Age, gender and handedness-matched participants between the age of 1 day to no upper limit.
Who may be able to join
- Patient has confirmation of a WFS1 mutation OR
- Both of the following conditions:
- diabetes mellitus requiring insulin and
- optic nerve atrophy diagnosed by a physician.
- Biological or non-biological parent/caregiver (proxy) of a participant.
Who cannot join
- Patient 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 the use of a ventilator or inability to walk.
- Sibling Group: Biological, half and step-siblings who do not have any symptoms of WFS and/or have had genetic testing to show that they do not have WFS may participate.
- Inability of participant or guardian to understand informed consent.
- Proxy Group: Adult Biological parent(s), biological caregiver, or non-biological caregiver of adult and minor participants in any of the four groups.
- Proxy is unaware of the participant's diagnosis (as it applies).
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: International Tracking Neurodegeneration in Early Wolfram Syndrome
Wolfram syndrome (WFS; OMIM #222300) is a rare autosomal recessive disease clinically defined in 1938 as the combination of childhood-onset insulin dependent diabetes, optic nerve atrophy, diabetes insipidus and deafness. Based on early descriptions, neurological features were thought to appear later in the disease with death occurring in middle adulthood. Importantly, the major causative gene (WFS1) was identified in 1998. This discovery allowed researchers to determine that the WFS1 gene encodes the protein wolframin, which helps protect cells from endoplasmic reticulum (ER) stress-mediated apoptosis, potentially via intracellular calcium homeostasis. Pathogenic mutations in WFS1 can result in death or dysfunction of cells that are under high ER stress, such as insulin-producing pancreatic β cells, causing insulin dependent diabetes. In addition, knowing the causative gene has allowed researchers to identify patients by their WFS1 mutation rather than the classic set of symptoms, leading to the increasing realization that the WFS1-related phenotype (including neurologic symptoms) is much more variable than previously understood. The first iteration of this grant (HD070855 "Tracking Neurodegeneration in Early Wolfram Syndrome") contributed to this shift in understanding. In this time, the research team has built a successful annual research clinic for WFS, that has met or exceeded recruitment goals for patients and controls, validated a clinical severity rating scale for WFS, described an unexpectedly early neurophenotype of reduced balance, smell identification and ventral pons volume, identified alterations in traditional diffusion tensor imaging (DTI) metrics that suggest hypomyelination as a pervasive neuropathological feature of WFS and provided justification for the selection of two primary outcomes (visual acuity and ventral pons volume) in a newly funded clinical efficacy study in WFS (Barrett, PI).
Read the detailed description
In this new grant, researchers hypothesize that ER stress-related dysfunction could inhibit production of myelin during neurodevelopment in WFS, as active and developing oligodendrocytes (cells that produce myelin in the brain) are more vulnerable to ER stress than mature ones. However, standard DTI methods conflate inflammatory processes (which can also be associated with ER stress) in the extra-axonal space with metrics of axonal and myelin integrity, leading to potentially confounded measurements. The research team proposea to collect novel, validated diffusion sequences on a new state of the art MRI scanner (Siemens Prisma) and apply cutting-edge analysis approaches to measure white matter integrity throughout the brain and in the optic nerve, improving the ability to draw conclusions about axonal and myelin integrity over time. Researchers will assess WFS patients annually at our WU Wolfram Research Clinic using these methods.
Findings from this work may indicate future targets for brain-specific intervention, identify outcome measures or high-risk subgroups for clinical trials targeting neurological symptoms. These data will also greatly expand our understanding of the cross-sectional and longitudinal phenotype of WFS1-mutation related disorders, rather than classically defined Wolfram Syndrome. Such knowledge will have a significant impact on patients and families by allowing physicians to provide more accurate prognoses. Finally, forms of ER stress-mediated apoptosis have been implicated in more common neurodegenerative, endocrine and neurodevelopmental diseases, which may benefit from the insights gained here.
- Conditions
- Wolfram Syndrome
- Keywords
- Diabetes Mellitus, Diabetes Insipidus, Optic Atrophy, Deafness
- Medical subject headings
- Wolfram Syndrome, Diabetes Mellitus, Diabetes Insipidus, Optic Atrophy, Deafness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Wolfram Syndrome Patients | 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 | |
| Proxy Group | Adult Biological parent(s), biological caregiver or non-biological caregiver of adult and minor participants in the Wolfram group. These individuals report on symptoms of their family member with Wolfram. | |
| Siblings | Sibling Group: Biological, half and step-siblings who do not have any symptoms of WFS and/or have had genetic testing to show that they do not have WFS may participate. Exclusion Criteria: • Inability of participant or guardian to understand informed consent. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Regional Pons Volume
MRI measure of pons brain volume for Wolfram and sibling groups
Measured: last assessment in this longitudinal study, each participant was followed between 1 and 5 years.
Secondary outcomes (1)
Disease Severity Score
WURS physical severity score; rated by physician; range is 0 (no impairment) to 132 (most severe impairment)
Measured: last assessment in this longitudinal study, each participant was followed between 1 and 5 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2019
- Study start10 Aug 2018
- Primary completion31 Dec 2023
- Study completion31 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Wolfram SyndromeStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 128 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Tamara G Hershey, PhD, Principal investigator, Washington University Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03951298
- Sponsor's protocol ID
- 201808060
- Acronym
- I-TRACK
- Status last verified
- Sep 2026
- First submitted
- 13 May 2019
- Last updated
- 23 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- International Tracking Neurodegeneration in Early Wolfram Syndrome
- ClinicalTrials.gov ID
- NCT03951298
- Acronym / sponsor ID
- I-TRACK / 201808060
- Conditions
- Wolfram Syndrome
- Keywords
- Diabetes Mellitus, Diabetes Insipidus, Optic Atrophy, Deafness
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 128 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- 10 Aug 2018 (actual)
- Primary completion
- 31 Dec 2023 (actual)
- Study completion
- 31 Dec 2023 (actual)
- First posted
- 15 May 2019 (actual)
- Results
- Posted 23 Sep 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Wolfram syndrome (WFS; OMIM #222300) is a rare autosomal recessive disease clinically defined in 1938 as the combination of childhood-onset insulin dependent diabetes, optic nerve atrophy, diabetes insipidus and deafness. Based on early descriptions, neurological features were thought to appear later in the disease with death occurring in middle adulthood. Importantly, the major causative gene (WFS1) was identified in 1998. This discovery allowed researchers to determine that the WFS1 gene encodes the protein wolframin, which helps protect cells from endoplasmic reticulum (ER) stress-mediated apoptosis, potentially via intracellular calcium homeostasis. Pathogenic mutations in WFS1 can result in death or dysfunction of cells that are under high ER stress, such as insulin-producing pancreatic β cells, causing insulin dependent diabetes. In addition, knowing the causative gene has allowed researchers to identify patients by their WFS1 mutation rather than the classic set of symptoms, leading to the increasing realization that the WFS1-related phenotype (including neurologic symptoms) is much more variable than previously understood. The first iteration of this grant (HD070855 "Tracking Neurodegeneration in Early Wolfram Syndrome") contributed to this shift in understanding. In this time, the research team has built a successful annual research clinic for WFS, that has met or exceeded recruitment goals for patients and controls, validated a clinical severity rating scale for WFS, described an unexpectedly early neurophenotype of reduced balance, smell identification and ventral pons volume, identified alterations in traditional diffusion tensor imaging (DTI) metrics that suggest hypomyelination as a pervasive neuropathological feature of WFS and provided justification for the selection of two primary outcomes (visual acuity and ventral pons volume) in a newly funded clinical efficacy study in WFS (Barrett, PI).
Detailed description
In this new grant, researchers hypothesize that ER stress-related dysfunction could inhibit production of myelin during neurodevelopment in WFS, as active and developing oligodendrocytes (cells that produce myelin in the brain) are more vulnerable to ER stress than mature ones. However, standard DTI methods conflate inflammatory processes (which can also be associated with ER stress) in the extra-axonal space with metrics of axonal and myelin integrity, leading to potentially confounded measurements. The research team proposea to collect novel, validated diffusion sequences on a new state of the art MRI scanner (Siemens Prisma) and apply cutting-edge analysis approaches to measure white matter integrity throughout the brain and in the optic nerve, improving the ability to draw conclusions about axonal and myelin integrity over time. Researchers will assess WFS patients annually at our WU Wolfram Research Clinic using these methods.
Findings from this work may indicate future targets for brain-specific intervention, identify outcome measures or high-risk subgroups for clinical trials targeting neurological symptoms. These data will also greatly expand our understanding of the cross-sectional and longitudinal phenotype of WFS1-mutation related disorders, rather than classically defined Wolfram Syndrome. Such knowledge will have a significant impact on patients and families by allowing physicians to provide more accurate prognoses. Finally, forms of ER stress-mediated apoptosis have been implicated in more common neurodegenerative, endocrine and neurodevelopmental diseases, which may benefit from the insights gained here.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Wolfram Syndrome Patients | – | –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 |
| Proxy Group | – | –Adult Biological parent(s), biological caregiver or non-biological caregiver of adult and minor participants in the Wolfram group. These individuals report on symptoms of their family member with Wolfram. |
| Siblings | – | –Sibling Group: Biological, half and step-siblings who do not have any symptoms of WFS and/or have had genetic testing to show that they do not have WFS may participate. Exclusion Criteria: • Inability of participant or guardian to understand informed consent. |
Who may qualify
- Ages
- 1 day and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Age, gender and handedness-matched participants between the age of 1 day to no upper limit.
Key inclusion criteria (5 listed)
- Patient has confirmation of a WFS1 mutation OR
- Both of the following conditions:
- Biological or non-biological parent/caregiver (proxy) of a participant.
Key exclusion criteria (7 listed)
- Patient 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 the use of a ventilator or inability to walk.
- Sibling Group: Biological, half and step-siblings who do not have any symptoms of WFS and/or have had genetic testing to show that they do not have WFS may participate.
- Inability of participant or guardian to understand informed consent.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Regional Pons Volume
Time frame: last assessment in this longitudinal study, each participant was followed between 1 and 5 years.
MRI measure of pons brain volume for Wolfram and sibling groups
1 secondary outcome
Disease Severity Score
Time frame: last assessment in this longitudinal study, each participant was followed between 1 and 5 years.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Does Recessive Optic Atrophy Due to WFS1 Exist?
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Mechanisms of Fecal Incontinence in Wolfram Syndrome
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tamara G Hershey, PhD principal investigator
Washington University Medical School
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Wolfram Syndrome, run by Washington University School of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Sep 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Regional Pons Volume (time frame: last assessment in this longitudinal study, each participant was followed between 1 and 5 years.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2026.