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근긴장성 이영양증 유형 1(END-DM1)에서 바이오마커 및 임상 종점 확립

2026년 11월 2일 업데이트: Virginia Commonwealth University

Building on previous work of the Myotonic Dystrophy Clinical Research Network (DMCRN), the present study seeks to overcome insufficient data on natural history; lack of reliable biomarkers; and incomplete characterization and limited biological understanding of the phenotypic heterogeneity of Myotonic Dystrophy 1 by examining strategies to improve the reliability by making further refinements in our sample collection and analysis procedures by developing strategies for managing patient heterogeneity going forward.

Funding Source- FDA OOPD

연구 개요

상태

모병

정황

상세 설명

Approximately 700 adult participants (18 to 70 years old, inclusive) with DM1 will be enrolled at 15 centers (up to 70 patients will be recruited at each site). No treatment will be administered as part of this study. Participants will receive standard of care as determined by the investigators. Study visits occur at baseline/0 months, 12 months, and 24 months. Few restrictions are placed on participation in the study because the investigators aim to capture the full spectrum of disease severity.

Muscle biopsy sub-study: Studies of splicing biomarkers in muscle biopsy samples will be conducted on a subset of 95 participants. These participants will have an additional study visit at 3 months.

Longitudinal muscle biopsy sub-study: Up to 30 individuals who have had a prior muscle biopsy as part of a DMCRN study will be asked to undergo another biopsy greater than 24 months after the prior biopsy. These participants will have an additional ad hoc biopsy visit.

COVID-19 sub-study: To evaluate severity of illness and response to COVID-19 vaccination in DM1 patients compared to corresponding data available about the general population, END-DM1 study participants will be asked to complete a one-time survey about COVID-19 experiences. A subset of those participants' blood samples will be analyzed to understand immunoglobulin response to infection and vaccination in DM1 patients.

Actigraphy sub-study: To assess daily physical activity in individuals with DM1 and evaluate physical activity changes over a 12-24 month period related to disease progression, a subset of participants will be asked to wear a small, wireless activity monitor while performing functional assessments described in the main study. Those participants will be asked to wear the activity monitor for 7 days following their research visit. Those participants will be asked to complete additional questionnaires.

Handheld Dynamometry sub-study: To evaluate additional muscle strength methods, a subset of participants will be asked to complete additional strength testing using either the MEDup or MicroFET handheld dynamometry device on the same day as their END-DM1 main study visit. Those participants will be asked to return to the clinic for a second visit within 10 days of the END-DM1 study visit to repeat the handheld dynamometry assessments and complete additional strength measures.

연구 유형

관찰

등록 (추정된)

700

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 연락처

연구 연락처 백업

연구 장소

  • 네덜란드
  • 뉴질랜드
  • 독일
      • München, 독일
        • 모병
        • Friedrich Baur Institute, Ludwig-Maximilians-Universität München
        • 연락하다:
        • 수석 연구원:
          • Benedikt Schoser, FEAN
        • 연락하다:
  • 미국
    • California
      • La Jolla, California, 미국, 92703
      • Los Angeles, California, 미국, 90095
        • 모병
        • University of California, Los Angeles
        • 수석 연구원:
          • Perry Shieh, MD, PhD
        • 연락하다:
    • Colorado
      • Denver, Colorado, 미국, 80204
    • Florida
    • Iowa
      • Iowa City, Iowa, 미국, 52242
    • Kansas
      • Kansas City, Kansas, 미국, 66160
        • 모병
        • Kansas University Medical Center
        • 수석 연구원:
          • Jeffrey Statland, MD
        • 연락하다:
        • 연락하다:
    • New York
    • Ohio
      • Columbus, Ohio, 미국, 43210
    • Texas
      • Houston, Texas, 미국, 77030
        • 모병
        • Houston Methodist Neurological Institute
        • 수석 연구원:
          • Erika P. Greene
        • 연락하다:
    • Virginia
  • 영국
      • London, 영국
      • London, 영국
        • 모병
        • St. George's, University of London
        • 연락하다:
        • 수석 연구원:
          • Emma Matthews
  • 이탈리아
      • Milan, 이탈리아
        • 완전한
        • Centro Clinico NeMO
  • 캐나다
      • Québec, 캐나다
        • 모집하지 않고 적극적으로
        • Université de Sherbrooke

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

18년 (성인, 고령자)

건강한 자원 봉사자를 받아들입니다

아니

연구 대상 성별

모두

샘플링 방법

확률 샘플

연구 인구

DM1 has a prevalence rate of approximately 1 per 2,300. There are no expected gender differences. Both men and women will be selected for this study.

Children with DM1 are not included in this project because the pathophysiological basis of congenital and childhood DM1 appears to be mechanistically distinct.

설명

Inclusion criteria:

  • Age 18 to 70 (inclusive)
  • Competent to provide informed consent
  • Clinical diagnosis of DM1 based on research criteria1 or positive genetic test
  • Comment: The clinical research criteria 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.2

Exclusion criteria:

  • Symptomatic renal or liver disease, uncontrolled diabetes or thyroid disorder, or active malignancy other than skin cancer.
  • Current alcohol or substance abuse
  • Concurrent enrollment in clinical trial for DM1, or participation in trial within 6 months of entry.
  • 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.
  • Note: non-ambulatory participants are not excluded, but are limited to <15% of enrollment.

Inclusion criteria for participants in the muscle biopsy sub-study:

• Of the 95 patients undergoing the tibialis anterior muscle biopsy, at least half will have at least moderate weakness of ankle dorsiflexion, defined as MRC score ≤ 4+. This is in order to obtain a muscle tissue sample in a person more severely affected with myotonic dystrophy. Approximately 10 patients at each site will undergo the muscle biopsy.

Exclusion criteria for 95 participants in the muscle biopsy sub-study:

  • Known CTG repeat expansion size less than 100 repeats, unless there are clear cut signs of limb weakness and muscle wasting. This is in order to obtain a muscle tissue sample in a person more severely affected with myotonic dystrophy.
  • Use of anticoagulant such as warfarin or a direct oral anticoagulant (e.g. dabigatran) due to the increased risk of bleeding.
  • Use of aspirin or non-steroidal anti-inflammatory agents should be discontinued 3 days prior to the biopsy procedure, if possible.
  • Platelet count <50,000 (if known) due to the increased risk of bleeding.
  • History of a bleeding disorder due to the increased risk of bleeding.
  • Advanced wasting of tibialis anterior (TA) muscle that precludes needle muscle biopsy in order to ensure that a sample taken would be of muscle and not just fat and fascia.
  • Previous muscle biopsy of either TA in order to provide muscle tissue samples of non-biopsied muscles.

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 관찰 모델: OTHER
  • 시간 관점: PROSPECTIVE

코호트 및 개입

그룹/코호트
Study Visits

Patients will receive standard of care as determined by their treating physician. Study visits occur at baseline/0 months, 12 months, and 24 months

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Change in ambulation over 24 months as measured by the 10 meter walk (m/s).
기간: 12 and 24 months

10 meter walk will be measured (m/s)
12 and 24 months
Change in respiratory function over 24 months as measured by spirometry, specifically the supine forced vital capacity (FVC).
기간: 12 and 24 months

Supine forced vital capacity (% predicted)
12 and 24 months
Percent splicing of DM1-affected splice events
기간: 3 months

RNA sequenced of muscle biopsy samples collected at two different times will be combined and used to calculate a percent splicing index (PMI)
3 months

기타 결과 측정

결과 측정
측정값 설명
기간
Longitudinal Muscle Biopsy Sub-study: Characterization of RNA splicing measures over a prolonged period of time (>24 months)
기간: 24 months

RNA sequenced of muscle biopsy samples collected at two different times will be combined and used to calculate a percent splicing index (PMI)
24 months
Longitudinal Muscle Biopsy Sub-study: Characterization of functional endpoints over a prolonged period of time (>24 months)
기간: 24 months

10-meter walk/run, grip strength, ADF (ankle dorsiflexion) strength, supine FVC (forced vital capacity)
24 months
COVID-19 Sub-study: Data from DM1 patients or caregivers about COVID-19 illness and vaccination experience, severity of illness and response to vaccination in DM1 patients compared to corresponding data available about the general population.
기간: 24 months

To evaluate the severity and rate of COVID-19 infection in patients with DM1 compared to the general population symptomatic response to COVID-19 vaccination in DM1 patients
24 months
COVID-19 Sub-study: Immunoglobulin profile and measles titers, and COVID-19 IgG titers
기간: 24 months

To understand immunoglobulin response to infection and vaccination in DM1 patients
24 months
Actigraphy Sub-study: Feasibility of measuring daily physical activity in individuals with DM1 in a multi-site study
기간: 24 months

Participants will be asked to wear an activity monitor for 7 days following their in-clinic END-DM1 study visit to evaluate whether this type of activity monitoring is feasible in future trials.
24 months
Actigraphy Sub-study: Objective daily physical activity using wireless accelerometry (ActiGraph), and comparison to normative values and patient reported physical activity.
기간: 24 months

Participants will be asked to wear an activity monitor for 7 days following their in-clinic END-DM1 study visit and report physical activity, to establish physical activity data in the DM1 population.
24 months
Actigraphy Sub-study: Physical activity changes over a 12-24 month period related to disease progression.
기간: 24 months

Participants will wear the wireless activity monitor during the functional and strength measures, and complete additional study questionnaires at their regular END-DM1 study visits.
24 months
Handheld Dynamometry Sub-study: Inter-rater reliability, standard error of measurement, and minimal detectable change of Maximal Isometric Muscle Strength force values obtained with the MEDup and MicroFET handheld dynamometers in adults with DM1
기간: 24 months

Participants will be assessed using either the MEDup or MicroFET handheld dynamometer on the same day as an END-DM1 main study visit. Participants will complete a second visit +/- 10 days from that visit where HHD will be assessed using the same HHD method (either MEDup or MicroFET) used at the HHD visit. Additional functional and strength assessments will be captured at this visit.
24 months
Handheld Dynamometry Sub-study: Comparison of quantitative muscle strength testing feasibility and validity between MEDup and MicroFET with the existing Fixed-QMT currently used in the END-DM1 study protocol.
기간: 24 months

Data captured for MEDup and MicroFET will be compared to data collected using the Fixed-QMT measures in the main END-DM1 study.
24 months

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

Virginia Commonwealth University

협력자

Radboud University Medical Center
University College London Hospitals
University of California, Los Angeles
University of Iowa
University of Florida
Stanford University
Ohio State University
Ludwig-Maximilians - University of Munich
University of Rochester
The Methodist Hospital Research Institute
Fondazione Serena Onlus - Centro Clinico NeMO Milano

수사관

  • 수석 연구원: Nicholas Johnson, MD, Virginia Commonwealth University
  • 수석 연구원: Charles Thornton, MD, University of Rochester

간행물 및 유용한 링크

연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.

일반 간행물

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (실제)

2019년 1월 1일

기본 완료 (추정된)

2026년 12월 1일

연구 완료 (추정된)

2026년 12월 1일

연구 등록 날짜

최초 제출

2019년 6월 2일

QC 기준을 충족하는 최초 제출

2019년 6월 7일

처음 게시됨 (실제)

2019년 6월 11일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2026년 11월 3일

QC 기준을 충족하는 마지막 업데이트 제출

2026년 11월 2일

마지막으로 확인됨

2026년 11월 1일

추가 정보

이 연구와 관련된 용어

키워드

추가 관련 MeSH 약관

기타 연구 ID 번호

  • HM20014419
  • DMCRN (기타 식별자: University of Rochester)
  • FD-R-006071 (기타 보조금/기금 번호: OPD)

개별 참가자 데이터(IPD) 계획

개별 참가자 데이터(IPD)를 공유할 계획입니까?

아니요

IPD 계획 설명

Aggregated and deidentified data will be shared with qualified investigators upon majority approval of the DMCRN investigators.

약물 및 장치 정보, 연구 문서

미국 FDA 규제 의약품 연구

아니

미국 FDA 규제 기기 제품 연구

아니

이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .

구독하다