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Variability of Molecular Biomarkers and Clinical Measures in People With Myotonic Dystrophy Type 1

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by National Institutes of Health Clinical Center (CC)
University of Rochester, New York
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) ) Identifier:
First received: June 24, 2014
Last updated: NA
Last verified: May 2014
History: No changes posted


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.

Muscle Myopathies
Muscular Dystrophy
Inherited Neuromuscular Conditions

Study Type: Observational
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

Resource links provided by NLM:

Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • 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 ]

Estimated Enrollment: 24
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)
Detailed Description:

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.


Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

To be eligible to participate in this study, candidates must meet the following eligibility criteria at Visit 1:

  • Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information in accordance with national and local patient privacy regulations.
  • Men and women, 18 to 70 years old, inclusive; body mass index less than or equal to 33.
  • Onset of DM1 after age 10.
  • Clinical diagnosis of DM1 based on research criteria or prior genetic testing with confirmation of DMPK CTG repeat length greater than or equal to 70. Note that the number of patients with repeat lengths of 70 to 100 will be limited to 3 per site. A genetic test confirming DM1 is not required for entry. As discussed below, many individuals with DM1 who are followed in neuromuscular clinics have never had a genetic test, and genetic testing confirms DM1 in > 99% of individuals who meet clinical criteria. A DNA sample will be obtained from all subjects during the first study visit for DM1 mutation analysis. CTG repeat testing will be run even if subjects have previously had this tested. If this test does not show an expanded repeat in DMPK the subject will be withdrawn from the study.
  • Ability to complete a 6 minute walk test (ankle foot orthoses allowed, but cane and walker are not).


Candidates will be excluded from study entry if any of the following exclusion criteria exist at Visit 1 or at the time point specified in the individual criterion listed:

  • Clinically significant infections or medical illness from 30 days prior to Visit 1.
  • History of, or abnormal laboratory values indicative of, significant medical, neurologic (other than DM1), or psychiatric disorders that might preclude participation in the study in the opinion of the Investigator.
  • A recent history of any of the following conditions on routine blood screening: white blood cells < 3000, platelets < 100,000, hematocrit < 30%, symptomatic liver disease with serum albumin < 3 g/L, or creatinine > 1.5 mg%.
  • Any of the following medical conditions: uncontrolled or insulin dependent diabetes mellitus, congestive heart failure, symptomatic cardiomyopathy, symptomatic coronary artery disease, cancer (other than skin cancer) within the prior 5 years, multiple sclerosis, or other serious medical illness.
  • Myotonic dystrophy type 2 or other diseases that mimic the signs or symptoms of DM1. Coexistence of other neuromuscular disease.
  • Thyroid dysfunction that is untreated (if on thyroid hormone replacement therapy, need to have adequate and stable replacement over the previous 6 months).
  • Second or third degree heart block, atrial flutter, atrial fibrillation, ventricular tachycardia, or is receiving medication for the treatment of cardiac arrhythmia.
  • Liver or kidney disease requiring ongoing treatment.
  • Have a seizure disorder.
  • Drug or alcohol abuse within 3 months of Visit 1.
  • Women who are pregnant or breastfeeding or who plan to become pregnant during the study s duration.
  • Treatment with supplemental anabolic hormones (including testosterone, human recombinant growth hormone, human recombinant insulin like growth factor-1, other anabolic drug mixtures) during the previous 12 months.
  • History of bleeding tendency or ongoing oral anticoagulation.
  • Hypersensitivity to local anesthetics or components thereof to be used in the biopsy procedure.
  • Participation in any investigational treatment study within 6 months prior to Visit 1.
  • Inability or unwillingness to undergo any of the study-specific procedures or assessments, including needle muscle biopsies.
  • Medical or other unspecified reasons that in the opinion of the Investigator makes the patient unsuitable for enrollment.
  • Treatment with any of the following anti-myotonia medications within 8 weeks prior to the study entry and 1 year thereafter:

    • phenytoin
    • carbamazepine
  • procainamide

    • disopyramide
    • nifedipine
    • acetazolamide
    • clomipramine
    • imipramine
    • mexiletine
  • Treatment with corticosteroids within 8 weeks prior to Visit 1.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT02176798

Contact: Hirity Shimellis (301) 594-5442
Contact: Ami K Mankodi, M.D. (301) 827-6690

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   
Sponsors and Collaborators
University of Rochester, New York
Principal Investigator: Ami K Mankodi, M.D. National Institute of Neurological Disorders and Stroke (NINDS)
  More Information

Additional Information:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) ) Identifier: NCT02176798     History of Changes
Other Study ID Numbers: 140132, 14-N-0132
Study First Received: June 24, 2014
Last Updated: June 24, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Inherited Neuromuscular Condition
Muscular Dystrophy
Muscle Myopathies

Additional relevant MeSH terms:
Muscular Dystrophies
Myotonic Dystrophy
Genetic Diseases, Inborn
Heredodegenerative Disorders, Nervous System
Muscular Diseases
Muscular Disorders, Atrophic
Musculoskeletal Diseases
Myotonic Disorders
Nervous System Diseases
Neurodegenerative Diseases
Neuromuscular Diseases processed this record on November 20, 2014