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Protocol Details

A Multicenter Observational Study to Assess the Variability of Molecular Biomarkers and Clinical Measures in Patients with Myotonic Dystrophy Type 1

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

14-N-0132

Sponsoring Institute

National Institute of Neurological Disorders and Stroke (NINDS)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 18
Max Age: 70

Referral Letter Required

No

Population Exclusion(s)

Children

Special Instructions

Currently Not Provided

Keywords

Inherited Neuromuscular Condition;
Muscular Dystrophy;
Muscle Myopathies

Recruitment Keyword(s)

None

Condition(s)

Muscle Myopathies;
Muscular Dystrophy;
Inherited Neuromuscular Conditions

Investigational Drug(s)

None

Investigational Device(s)

None

Intervention(s)

None

Supporting Site

National Institute of Neurological Disorders and StrokeUniversity of Rochester, New York

Background:

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.

Objective:

To find the best ways to assess and measure how people are affected by DM1.

Eligibility:

Adults age 18 70 with DM1 that began after age 10.

Design:

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.

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Eligibility

INCLUSION CRITERIA:

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).

EXCLUSION CRITERIA:

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.

VALIDITY SUB STUDY:

INCLUSION CRITERIA:

-DM1 patients

-Age 18 to 70 (inclusive)

-Clinical or genetic diagnosis of myotonic dystrophy type-1

-Disease Controls:

--Age 18 to 70 (inclusive)

--Clinical or genetic diagnosis of other inherited muscle disorder including myotonic dystrophy type 2, non-dystrophic myotonia, spinal and bulbar muscular atrophy and ALS 4

Healthy Volunteers:

--Age 18 to 70 (inclusive)

--Must be unaffected by a neuromuscular condition

--Must not have any family members diagnosed with a neuromuscular disorder

EXCLUSION CRITERIA:

-Treatment with any of the following anti-myotonia medications within 8 weeks prior to the study entry:

--phenytoin

--carbamazepine

--procainamide

--disopyramide

--nifedipine

--acetazolamide

--clomipramine

--imipramine

--mexiletine

-Thyroid dysfunction (if on thyroid hormone replacement therapy, need to have adequate and stable replacement over the previous 6 months)

-Participation in any investigational treatment study within 6 months prior to visit

-Inability or unwillingness to undergo any of the study-specific procedures or assessments

-Inability to understand the purpose and risks of the study and provide signed informed consent

MRI EXCLUSION CRITERIA:

-Having metal objects in his body that are not MRI-safe. These include the following objects: 1) pacemakers or other implanted electrical devices; 2) brain stimulators; 3) some types of dental implants; 4) aneurysm clips (metal clips on the wall of a large artery); 5) metallic prostheses (including metal pins and rods, heart valves, and cochlear implants; 6) implanted delivery pump; 7) permanent eye liner; or 8) shrapnel fragments.

-Having a fear of closed spaces

-Women who are pregnant or breastfeeding


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Citations:

Mankodi A, Logigian E, Callahan L, McClain C, White R, Henderson D, Krym M, Thornton CA. Myotonic dystrophy in transgenic mice expressing an expanded CUG repeat. Science. 2000 Sep 8;289(5485):1769-73.

Osborne RJ, Thornton CA. RNA-dominant diseases. Hum Mol Genet. 2006 Oct 15;15 Spec No 2:R162-9.

Brook JD, McCurrach ME, Harley HG, Buckler AJ, Church D, Aburatani H, Hunter K, Stanton VP, Thirion JP, Hudson T, et al. Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3' end of a transcript encoding a protein kinase family member. Cell. 1992 Feb 21;68(4):799-808. Erratum in: Cell. 1992 Apr 17;69(2):385.

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Contacts:

Principal Investigator

Referral Contact

For more information:

Ami K. Mankodi, M.D.
National Institute of Neurological Disorders and Stroke (NINDS)
BG 35 RM 2A1002
35 CONVENT DR
BETHESDA MD 20814
(301) 827-6690
ami.mankodi@nih.gov

Hirity Shimellis, CCRC
National Institute of Neurological Disorders and Stroke (NINDS)
National Institutes of Health
Building 10
Room 5S215
10 Center Drive
Bethesda, Maryland 20892
(301) 594-5442
hirity.shimellis@nih.gov

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: 1-866-411-1010
PRPL@cc.nih.gov

Clinical Trials Number:

NCT02176798

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