Brain Structure and Clinical Endpoints in Myotonic Dystrophy Type 2

NCT05854433 | Recruiting

• 2 other identifiers: IRB00065459K23NS125110-01A1
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Nearly two-third of patients with myotonic dystrophy type 2 (DM2) report that impaired cognition is among the most disabling symptoms and deeply affects their quality of life. Yet, relatively little is known about how DM2 affects brain structure and cognitive function as brain imaging studies in DM2 are extremely limited. This is a prospective, cross-sectional study of brain structure and function on cognitive and motor performance in patients with DM2 \& DM1 compared to healthy controls. All participants will undergo magnetic resonance imaging (MRI) to evaluate brain structure and white matter integrity, a comprehensive battery of cognitive and motor measures, self-reported questionnaires, and blood collection for brain-based biomarker analysis. A subset of participants will undergo lumbar puncture for cerebrospinal fluid (CSF) collection for additional biomarker analysis and validation. This work is critical to inform the development of rigorous clinical trial designs and plan for a longitudinal study to evaluate MRI measures as imaging biomarkers of disease progression and therapeutic response in DM2 \& DM1.

Conditions

Myotonic Dystrophy Type 2; Myotonic Dystrophy Type 1

Keywords

myotonic dystrophy; muscular dystrophy; cognitive dysfunction; memory; brain; central nervous system; MRI; biomarkers; white matter; neurodegenerative diseases

Outcome Measures

Primary Outcomes (4)

• Measures of voxel-based brain morphometry

  Measures of brain volume will be expressed as a ratio (0 to 1) to intracranial volume to create proportional values of brain volume.

  Baseline

• Fractional Anisotropy (FA)

  FA is an index of non-uniform movement of water molecules ranging from 0 to 1. Higher values of FA indicate healthy, dense, and well-organized white matter fibers. Lower values of FA indicate less healthy white matter track.

  Baseline

• Radial Diffusivity (RD)

  The value of apparent water diffusion coefficient in the direction perpendicular to the axonal fibers. The higher RD value indicates high dispersion of water and poorly-organized white matter fibers.

  Baseline

• Axial Diffusivity (AD)

  The value of apparent water diffusion coefficient in the direction lying along with the axonal fibers. The higher AD value indicates greater extracellular water content consecutively to the impaired white-matter fibers health, and to alterations of axonal water content

  Baseline

Secondary Outcomes (30)

• NIH-Toolbox (TB) Cognitive Measures: Executive Function Domain Scores

  Baseline

• NIH-TB: Executive Function/Attention Domain Scores

  Baseline

• NIH-TB: Processing Speed Domain Scores

  Baseline

• NIH-TB: Language Domain Scores

  Baseline

• NIH-TB: Working Memory Domain Scores

  Baseline

Study Arms (2)

Myotonic dystrophy types 1 and 2

Adults with myotonic dystrophy types 1 and 2 who meet all inclusion and exclusion criteria for the study. To be assessed at the baseline visit: Medical history and a focused neurological examination, brain MRI, a comprehensive Clinical Assessment Battery (CAB) of cognitive and motor measures, self-reported questionnaires, strength and motor function evaluation, and blood drawn for biomarker analysis. A subset of the participants who agree to have cerebrospinal fluid (CSF) collection for additional biomarker analysis will undergo lumbar puncture procedure.

Other: Non-interventional study

Controls

Healthy individuals who meet all inclusion and exclusion criteria for healthy controls. To be assessed at the baseline visit: Medical history and a focused neurological examination, brain MRI, a comprehensive Clinical Assessment Battery (CAB) of cognitive and motor measures, self-reported questionnaires, strength and motor function evaluation, and blood drawn for biomarker analysis. A subset of the participants who agree to have cerebrospinal fluid (CSF) collection for additional biomarker analysis will undergo lumbar puncture procedure.

Other: Non-interventional study

Interventions

Non-interventional study OTHER

No intervention will be administered as part of this study.

Controls; Myotonic dystrophy types 1 and 2

Eligibility Criteria

• Age: 30 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Myotonic dystrophy is a rare disease with an estimated prevalence rate of 12.5/100,000 in both myotonic dystrophy type 1 (DM1) and DM2. There are no expected gender differences. Both men and women will be selected for this study.

You may qualify if:

• Age 30-65 years old
• Diagnosis of DM1 or DM2 is based on genetic testing and/or clinical criteria. If the diagnosis is based on clinical criteria, positive DM2 genetic testing is required in first-degree relatives
• Symptoms or clinical findings of proximal muscle weakness
• Ambulate independently (a cane or walking stick is permitted)
• Able to provide informed consent for participation in the study
• Only individuals who are 30-65 years old will be eligible to participate for the full study protocol
• Diagnosis of adult-onset DM1 is based on genetic testing or clinical criteria. If the diagnosis is based on clinical criteria, positive DM1 genetic testing is required in first-degree relatives
• The onset of first symptoms must be between the 2nd and 4th decades of life
• Symptoms or clinical findings of distal muscle weakness and myotonia
• Ambulate independently (a cane or walking stick is permitted)
• Able to provide informed consent for participation in the study

You may not qualify if:

• Congenital or juvenile-onset DM1 (onset of first symptom \< 20-year-old)
• Individuals with a prior diagnosis of dementia, seizure, stroke, multiple sclerosis, Parkinson's Disease, or other neurodegenerative diseases
• Individuals with active psychiatric illness or alcohol/substance abuse.
• On medications with substantial sedative or cognitive side effects unless the doses have been stable for at least 3 months before the study visit.
• Inability or unwillingness to give written informed consent.
• Individuals with a pacemaker, defibrillator, or metal implanted that is contraindicated for MRI
• Individuals who are claustrophobic
• Individuals with a prior diagnosis of dementia, seizure, stroke, multiple sclerosis, Parkinson's Disease, or other neurodegenerative diseases
• Individuals with active psychiatric illness, alcohol or substance abuse, or dependence
• Individuals with a pacemaker, defibrillator, or metal implanted that is contraindicated for MRI
• Individuals who are claustrophobic
• Major medical illness which would prevent safe testing of MRI or motor function.
• On medications with substantial sedative or cognitive side effects unless the doses have been stable over the last 3 months before the study visit
• pregnancy
• Weight \> 400 pounds as the participant could not be properly positioned on the MRI table

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

blood (plasma and serum) collection cerebrospinal fluid (CSF) collection

MeSH Terms

Conditions

Myotonic Dystrophy; Muscular Dystrophies; Cognitive Dysfunction; Neurodegenerative Diseases

Condition Hierarchy (Ancestors)

Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Myotonic Disorders; Heredodegenerative Disorders, Nervous System; Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• Araya Puwanant, MD, MS

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Constance Linville

CONTACT

336-716-4568; clinvill@wakehealth.edu

Study Design

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

Study Record Dates

• First Submitted: April 21, 2023
• First Posted: May 11, 2023
• Study Start: April 26, 2023
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: February 2, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)