Variability of Molecular Biomarkers and Clinical Measures in People With Myotonic Dystrophy Type 1
Myotonic dystrophy type 1 (DM1) is a progressive disease that affects muscles in the lower legs, hands, neck, and face and also heart, brain, and other body organs. Researchers want to learn more about how DM1 affects the muscles, the digestive system, the heart, and the brain.
To find the best ways to assess and measure how people are affected by DM1.
Adults age 18 70 with DM1 that began after age 10.
The study will involve 3 visits at the NIH Clinical Center.
Each visit will involve different tests throughout the day.
- Visit 1 procedures:
- Participants will have a medical history taken and a physical exam. They will have blood and urine taken. Women of childbearing potential will take a urine pregnancy test.
- Participants will have an electrocardiogram. It records the electrical activity of the heart.
- Participants will complete 3 questionnaires about how their disease affects them.
- Participants will take a computerized test to assess alertness, problem-solving, and memory.
- Participants will take muscle strength tests during which they will walk, pull, push, and grip. The electrical activity of a leg muscle will be recorded.
- Participants will have Dual Energy X-ray Absorptiometry (DEXA). The DEXA machine will scan the participant s body while they lie on a table.
- A needle muscle biopsy will be performed. A needle will take small pieces of muscle from the front of the participant s leg.
- Visit 2 will take place 3 months after visit 1. Visit 1 procedures will be repeated. Participants will be given a grip strength meter to use from home.
- After visit 2, participants will call an automated telephone number daily for 30 days to report their symptoms and grip strength.
- Visit 3 will take place 12 months after visit 1. Visit 1 procedures will be repeated, except for the biopsy. This visit will mark the end of participation in the study.
Inherited Neuromuscular Conditions
|Study Design:||Time Perspective: Prospective|
|Official Title:||A Multicenter Observational Study to Assess the Variability of Molecular Biomarkers and Clinical Measures in Patients With Myotonic Dystrophy Type 1|
- To evaluate the stability of muscle biopsy RNA splice events over a 3 month period as potential biomarkers for use in future DM1 therapeutic trials [ Time Frame: ongoing ] [ Designated as safety issue: No ]
|Study Start Date:||June 2014|
|Estimated Study Completion Date:||January 2016|
|Estimated Primary Completion Date:||January 2016 (Final data collection date for primary outcome measure)|
Objective: Myotonic dystrophy type 1 (DM1) is one of the most prevalent inherited neuromuscular disorders that leads to severe disability and premature death. DM1 is caused by toxic effects of mutant RNA, which involve sequestration of splicing factors and consequent abnormal splicing of genes expressed in skeletal muscle. There is no effective therapy for DM1. However, recent studies suggest that DM1 may respond to RNA targeted therapies. With the promise of new therapies in DM1, there is a need for natural history data, clinical endpoints, and biomarkers to support the design and implementation of clinical trials. The goal of the current study is to prospectively assess the variability of clinical measures and molecular biomarkers of DM1 disease severity in multicenter studies.
Study population: We aim to screen up to 29 adult DM1 patients (18 to 70 years old, inclusive) at the NIH for enrollment in the study. Approximately 100 adult patients with DM1 will be enrolled at 6 study sites.
Design: Patients will report to the NIH study site for 3 visits: screening/baseline (Visit 1), 3 months plus or less 2 weeks (Visit 2), and 12 months plus or less 4 weeks (Visit 3). No treatment will be administered as part of this study. Patients will receive standard care as determined by their treating physician.
Outcome measures: The primary outcome measures are the mean and variance of the biomarker values, i.e., ratio of 2 alternative splice products from the same gene, in skeletal muscle at baseline and 3 months and the change from baseline (see Appendix B). The secondary outcome measures are the mean and variance at baseline, 3 months, and 12 months for (1) myotonia, (2) muscle strength and (3) patient perception of disease burden. Exploratory outcome measures include assessment of mean and variance of the following measures at baseline, 3 months and 12 months: (1) muscle function (2) whole body muscle mass by dual-energy X-ray absorptiometry (DEXA) scan, (3) quality of life, (4) the following measures of cognitive function: (i) Detection task (processing speed), (ii) Groton Maze Learning Test (executive function), (iii) One Back task (working memory), (iv) Identification task (visual attention), and (5) correlation analysis between the RNA biomarkers of aberrant splicing and the strength of the tibialis anterior (TA) muscle as measured by manual and quantitative muscle testing as well as ankle intellistretch device. In addition, serum and plasma may be analyzed for exploratory RNA and protein biomarkers.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02176798
|Contact: Hirity Shimellis||(301) firstname.lastname@example.org|
|Contact: Ami K Mankodi, M.D.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL) 800-411-1222 ext TTY8664111010 firstname.lastname@example.org|
|Principal Investigator:||Ami K Mankodi, M.D.||National Institute of Neurological Disorders and Stroke (NINDS)|