Establishing Biomarkers and Clinical Endpoints in Myotonic Dystrophy Type 1 (END-DM1) Extension (END-EXT)
Studienübersicht
Status
Status
Bedingungen
Bedingungen
Detaillierte Beschreibung
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?
Studientyp
Studientyp
Einschreibung (Geschätzt)
Einschreibung
Kontakte und Standorte
Studienkontakt
Studienkontakt
- Name: Jennifer Raymond
- Telefonnummer: 804-828-6318
- E-Mail: Jennifer.raymond@vcuhealth.org
Studieren Sie die Kontaktsicherung
- Name: Ruby Langeslay
- Telefonnummer: 804-828-6318
- E-Mail: Ruby.langeslay@vcuhealth.org
Studienorte
-
-
Virginia
-
Richmond, Virginia, Vereinigte Staaten, 23298
- Rekrutierung
- Virginia Commonwealth University
-
Hauptermittler:
- Nicholas Johnson, MD
-
Kontakt:
- Jennifer Raymond
- Telefonnummer: 804-828-6318
- E-Mail: Jennifer.raymond@vcuhealth.org
-
-
Teilnahmekriterien
Zulassungskriterien
Zulassungskriterien
Studienberechtigtes Alter
- Erwachsene
- Älterer Erwachsener
Akzeptiert gesunde Freiwillige
Probenahmeverfahren
Studienpopulation
Beschreibung
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.
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
Anzahl der Gruppen / Kohorten
Kohorten und Interventionen
Gruppe / KohorteGruppe / 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.
|
Was misst die Studie?
Primäre Ergebnismessungen
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Characterize the long-term disease progression- 10 meter walk/run
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
|
Mitarbeiter und Ermittler
Sponsor
Sponsor
Mitarbeiter
Mitarbeiter
Ermittler
Ermittler
- Hauptermittler: Nicholas Johnson, MD, Virginia Commonwealth University
Publikationen und hilfreiche Links
Allgemeine Veröffentlichungen
- 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.
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn (Geschätzt)
Studienbeginn
Primärer Abschluss (Geschätzt)
Primärer Abschluss
Studienabschluss (Geschätzt)
Studienabschluss
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Tatsächlich)
Zuerst gepostet
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes Update gepostet
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
- Neurologische Manifestationen
- Erkrankungen des Bewegungsapparates
- Erkrankungen des Nervensystems
- Muskelerkrankungen
- Neuromuskuläre Manifestationen
- Genetische Krankheiten, angeboren
- Neurodegenerative Krankheiten
- Heredodegenerative Erkrankungen, Nervensystem
- Muskelerkrankungen, atrophisch
- Myotonische Störungen
- Angeborene, erbliche und neonatale Krankheiten und Anomalien
- Pathologische Zustände, Anzeichen und Symptome
- Anzeichen und Symptome
- Muskeldystrophien
- Myotone Dystrophie
- Myotonie
- Neuromuskuläre Erkrankungen
Andere Studien-ID-Nummern
Andere Studien-ID-Nummern
- HM300000528 END-EXT
Arzneimittel- und Geräteinformationen, Studienunterlagen
Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt
Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt
Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .