- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT07700225
Establishing Biomarkers and Clinical Endpoints in Myotonic Dystrophy Type 1 (END-DM1) Extension (END-EXT)
8. juli 2026 opdateret af: Virginia Commonwealth University
Myotonic Dystrophy type 1 (DM1) is an autosomal dominant multisystemic disorder that causes progressive disability and shortened life expectancy.
It is characterized by progressive weakness and myotonia, which preferentially affects the craniofacial, hand, and distal leg muscles.
Many patients also experience difficulties with cognition, cardiac arrhythmias, respiratory failure, or cataracts.
Currently there is no treatment to slow progression or reverse the symptoms.
Studieoversigt
Status
Rekruttering
Detaljeret beskrivelse
The goal of this observational study is to characterize long-term disease progression over at least 4 years in at least 1,000 adults with myotonic dystrophy type 1 (DM1).
The main questions this study aims to answer are:
- How do clinical measures, such as walking speed, hand function, and muscle strength, change over a multi-year period in people with DM1?
- Can long-term changes in slowly progressive measures, like heart rhythms (ECG) and lung function (FVC), be accurately captured and used as biomarkers for the disease over time?
Undersøgelsestype
Observationel
Tilmelding (Anslået)
1000
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiekontakt
- Navn: Jennifer Raymond
- Telefonnummer: 804-828-6318
- E-mail: Jennifer.raymond@vcuhealth.org
Undersøgelse Kontakt Backup
- Navn: Ruby Langeslay
- Telefonnummer: 804-828-6318
- E-mail: Ruby.langeslay@vcuhealth.org
Studiesteder
-
-
Virginia
-
Richmond, Virginia, Forenede Stater, 23298
- Rekruttering
- Virginia Commonwealth University
-
Ledende efterforsker:
- Nicholas Johnson, MD
-
Kontakt:
- Jennifer Raymond
- Telefonnummer: 804-828-6318
- E-mail: Jennifer.raymond@vcuhealth.org
-
-
Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
- Voksen
- Ældre voksen
Tager imod sunde frivillige
Ingen
Prøveudtagningsmetode
Ikke-sandsynlighedsprøve
Studiebefolkning
The study seeks to enroll at least 1000 men and women aged 18 to 70 with a positive genetic test for myotonic dystrophy type 1, a clinical diagnosis of myotonic dystrophy type 1, or a clinical diagnosis or positive genetic test for congenital myotonic dystrophy.
based on research criteria.
Few restrictions are placed on participation in the study because we aim to capture the full spectrum of disease severity.
Beskrivelse
Inclusion Criteria:
- Age 18 to 70 years (inclusive)
- Written, voluntary informed consent must be obtained prior to any study procedures. In cases where a Legally Authorized Representative (LAR) provides consent, verbal assent will be obtained from the subject, as determined by the investigator and documented directly on the consent form. Capacity to consent will be determined by the neurologist at the Baseline visit and will be signed off on the Inclusion/Exclusion checklist.
- Clinical diagnosis of DM1 based on research criteria or positive genetic test. The research criteria for clinical diagnosis of DM1 require myotonia, muscle weakness in a characteristic distribution, and history of similar findings in a first degree relative. Genetic testing confirmed the diagnosis of DM1 in > 99% of individuals who satisfied these criteria. OR A diagnosis of CDM, which is defined as children having symptoms of myotonic dystrophy in the newborn period (<30 days), such as hypotonia, feeding or respiratory difficulty, requiring hospitalization to a ward or to the neonatal intensive care unit for 3 days or more; and a genetic test suspicious of an expanded trinucleotide (CTG) repeat in the DMPK gene in the child or first degree relative. An expanded CTG repeat size in the child is considered greater than 200 repeats or E1-E4 classification (E1= 200-500, E2=500-1,000, E3=1,000-1,500, E4>1,500)
Exclusion Criteria:
- Symptomatic renal or liver disease, uncontrolled diabetes or thyroid disorder, or active malignancy other than in situ skin cancer.
- Current alcohol or substance use disorder.
- Concurrent pregnancy or planned pregnancy during the course of the study.
- Concurrent medical condition that would, in the opinion of the investigator or clinical evaluator. compromise performance on study measures.
- Use of mexiletine or other anti-myotonia agents within 72 hours of any study visit.
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
Kohorter og interventioner
Gruppe / kohorte |
|---|
|
Myotonic Dystrophy Type 1 (DM1) Longitudinal Cohort
Participants with a clinical or genetic diagnosis of myotonic dystrophy type 1 (DM1) or congenital myotonic dystrophy (CDM).
This cohort includes individuals transitioning from the parent study, Establishing Biomarkers and Clinical Endpoints in Myotonic Dystrophy Type 1 (END-DM1; NCT03981575), as well as newly enrolled participants.
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Characterize the long-term disease progression- 10 meter walk/run
Tidsramme: Baseline (0 months), every 12 months over four years
|
The 10-meter walk test (10MWT) is used in research to reliably measure gait speed, assessing functional mobility and detecting changes in walking performance over time.
It is a highly reliable, quick, and cost-effective tool. .
It is favored for its simplicity, speed, and ability to predict functional independence.
A "good" score varies by age/condition, with healthy adults averaging over 1.2-1.4
m/s.
|
Baseline (0 months), every 12 months over four years
|
|
Characterize the long-term disease progression- vHOT
Tidsramme: Baseline (0 months), every 12 months over four years
|
The Video Hand Opening Time (vHOT) is used in research as a practical, low-cost, and reliable quantitative tool to measure handgrip myotonia (delayed muscle relaxation) in Myotonic Dystrophy Type 1 (DM1) patients.
It is particularly valuable for multicenter clinical trials because it allows for blinded, objective assessment of therapeutic responses.
A "good" (healthy) score is generally as close to zero as possible.
|
Baseline (0 months), every 12 months over four years
|
|
Characterize the long-term disease progression- grip strength
Tidsramme: Baseline (0 months), every 12 months over four years
|
Grip strength is used in research as a reliable, low-cost biomarker for overall muscle strength, aging, and mortality risk.
A good score varies by age and sex, with healthy young adults often averaging over 40-45 kg (males) and 25-30kg (females).
|
Baseline (0 months), every 12 months over four years
|
|
Characterize the long-term disease progression- ECG
Tidsramme: Baseline (0 months), every 12 months over four years
|
Electrocardiograms (ECGs/EKGs) are used in research for their non-invasive, cost-effective ability to track heart rhythm, diagnose cardiac conditions, and assess cardiovascular disease risk.
In research, a "good" ECG score indicates normal sinus rhythm and intervals, such as a PR interval of 120-200 milliseconds and an RR interval of 0.6-1.2
seconds.
|
Baseline (0 months), every 12 months over four years
|
|
Characterize the long-term disease progression- FVC
Tidsramme: Baseline (0 months), every 12 months over four years
|
Forced Vital Capacity (FVC) is crucial in research for diagnosing and tracking restrictive lung diseases (e.g., pulmonary fibrosis), assessing disease progression, and measuring treatment efficacy in clinical trials.
A "good" or normal FVC is typically 80% or higher of the predicted value, based on a patient's age, height, sex, and ethnicity.
|
Baseline (0 months), every 12 months over four years
|
|
Characterize the long-term disease progression- DM1-Activ-c
Tidsramme: Baseline (0 months), every 12 months over four years
|
The DM1-Activ-c (25-item) is a validated, Rasch-built, patient-reported outcome measure designed specifically to assess daily activity and participation in Myotonic Dystrophy Type 1 (DM1) patients.
It is used in research for its high sensitivity to disease progression and therapeutic changes (responsiveness), making it a reliable primary endpoint for clinical trials to measure patient improvement.
The DM1-Activ-c is scored on a scale from 0 to 100, where higher scores indicate better functional ability.
|
Baseline (0 months), every 12 months over four years
|
Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
Efterforskere
- Ledende efterforsker: Nicholas Johnson, MD, Virginia Commonwealth University
Publikationer og nyttige links
Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.
Generelle publikationer
- Guyatt GH, Osoba D, Wu AW, Wyrwich KW, Norman GR; Clinical Significance Consensus Meeting Group. Methods to explain the clinical significance of health status measures. Mayo Clin Proc. 2002 Apr;77(4):371-83. doi: 10.4065/77.4.371.
- Jaeschke R, Singer J, Guyatt GH. Measurement of health status. Ascertaining the minimal clinically important difference. Control Clin Trials. 1989 Dec;10(4):407-15. doi: 10.1016/0197-2456(89)90005-6.
- Mathai SC, Puhan MA, Lam D, Wise RA. The minimal important difference in the 6-minute walk test for patients with pulmonary arterial hypertension. Am J Respir Crit Care Med. 2012 Sep 1;186(5):428-33. doi: 10.1164/rccm.201203-0480OC. Epub 2012 Jun 21.
- Goldman A, Ramsay M, Jenkins T. Ethnicity and myotonic dystrophy: a possible explanation for its absence in sub-Saharan Africa. Ann Hum Genet. 1996 Jan;60(1):57-65. doi: 10.1111/j.1469-1809.1996.tb01172.x.
- Griggs RC, Wood DS. Criteria for establishing the validity of genetic recombination in myotonic dystrophy. Neurology. 1989 Mar;39(3):420-1. doi: 10.1212/wnl.39.3.420. No abstract available.
- Personius KE, Pandya S, King WM, Tawil R, McDermott MP. Facioscapulohumeral dystrophy natural history study: standardization of testing procedures and reliability of measurements. The FSH DY Group. Phys Ther. 1994 Mar;74(3):253-63. doi: 10.1093/ptj/74.3.253.
- Thornton CA, Johnson K, Moxley RT 3rd. Myotonic dystrophy patients have larger CTG expansions in skeletal muscle than in leukocytes. Ann Neurol. 1994 Jan;35(1):104-7. doi: 10.1002/ana.410350116.
- Braida C, Stefanatos RK, Adam B, Mahajan N, Smeets HJ, Niel F, Goizet C, Arveiler B, Koenig M, Lagier-Tourenne C, Mandel JL, Faber CG, de Die-Smulders CE, Spaans F, Monckton DG. Variant CCG and GGC repeats within the CTG expansion dramatically modify mutational dynamics and likely contribute toward unusual symptoms in some myotonic dystrophy type 1 patients. Hum Mol Genet. 2010 Apr 15;19(8):1399-412. doi: 10.1093/hmg/ddq015. Epub 2010 Jan 15.
- Guyatt G, Walter S, Norman G. Measuring change over time: assessing the usefulness of evaluative instruments. J Chronic Dis. 1987;40(2):171-8. doi: 10.1016/0021-9681(87)90069-5.
- Wyrwich KW, Tierney WM, Wolinsky FD. Further evidence supporting an SEM-based criterion for identifying meaningful intra-individual changes in health-related quality of life. J Clin Epidemiol. 1999 Sep;52(9):861-73. doi: 10.1016/s0895-4356(99)00071-2.
- Teng S, Wang B, Yang F, Yi X, Zhang X, Sun Y. MediDRNet: Tackling category imbalance in diabetic retinopathy classification with dual-branch learning and prototypical contrastive learning. Comput Methods Programs Biomed. 2024 Aug;253:108230. doi: 10.1016/j.cmpb.2024.108230. Epub 2024 May 17.
- Liu P, Liu Y, Liu H, Xiong L, Mei C, Yuan L. A Random Forest Algorithm for Assessing Risk Factors Associated With Chronic Kidney Disease: Observational Study. Asian Pac Isl Nurs J. 2024 Jun 3;8:e48378. doi: 10.2196/48378.
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart (Anslået)
1. juli 2026
Primær færdiggørelse (Anslået)
1. december 2032
Studieafslutning (Anslået)
1. december 2032
Datoer for studieregistrering
Først indsendt
8. juli 2026
Først indsendt, der opfyldte QC-kriterier
8. juli 2026
Først opslået (Faktiske)
13. juli 2026
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
13. juli 2026
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
8. juli 2026
Sidst verificeret
1. juli 2026
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
- Neurologiske manifestationer
- Muskuloskeletale sygdomme
- Sygdomme i nervesystemet
- Muskelsygdomme
- Neuromuskulære manifestationer
- Genetiske sygdomme, medfødte
- Neurodegenerative sygdomme
- Heredodegenerative lidelser, nervesystem
- Muskellidelser, atrofisk
- Myotoniske lidelser
- Medfødte, arvelige og neonatale sygdomme og abnormiteter
- Patologiske tilstande, tegn og symptomer
- Tegn og symptomer
- Muskeldystrofier
- Myotonisk dystrofi
- Myotoni
- Neuromuskulære sygdomme
Andre undersøgelses-id-numre
- HM300000528 END-EXT
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
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Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .