Retrospective Natural History Study of Infants and Toddlers With LAMA2-CMD

NCT04299321 | Completed

• 1 other identifier: PRO-LAMA2-001
• Study Type: observational
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

This retrospective chart review study of 75-120 LAMA2-CMD patients will expand the investigators understanding of the natural history of this disease. Current and pending publications cover research performed only in ages 5-16 years; there is currently no documented natural history for patients ages 0-5 years. Data collected in this study has the potential to inform the design of future interventional studies that draw nearer to clinical trial readiness every day.

Conditions

Merosin Deficient Congenital Muscular Dystrophy

Keywords

LAMA2; LAMA2-CMD; CMD; MDC1A; LAMA2-MD; Merosin Deficient

Outcome Measures

Primary Outcomes (1)

• To characterize the natural history of LAMA2-CMD

  To characterize aspects of LAMA2-CMD in ages 0-5 years through medical chart review/data extraction, and participant survey. This study aims to derive clinical trial endpoints useful in conducting interventional trials in the near future.

  Birth to 5 years of age

Secondary Outcomes (2)

• To identify potential prognostic variables of LAMA2-CMD

  Birth to 5 years of age

• To identify disease symptoms associated with LAMA2-CMD that warrant monitoring and potential preventative measures

  Birth to 5 years of age

Eligibility Criteria

• Age: 2 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Infants and toddlers affected by LAMA2-CMD

You may qualify if:

• Patients diagnosed with LAMA2-CMD through:
• genetic confirmation of two (2) pathogenic mutations in LAMA2 -OR-
• genetic confirmation of one (1) pathogenic mutation in LAMA2, and supporting clinical phenotype based on two or more of the following: physical examination, brain imaging, muscle imaging, muscle biopsy, and creatine kinase (CK) levels (blood test)
• Patients may be living or deceased
• Patients may be male or female
• Patients with available medical records between 2000-2017, documenting diagnosis, observation, and treatment between ages 0-5 years and a minimum set of data covering 12-24 months during this age period.
• Patients with medical charts available in English
• Patients (or Parents of minor patients) who are able to consent to participation in English or Spanish, either directly, or through their own trusted interpreter
• Patients between the ages of 8-17 years who are able to provide assent to participation in English or Spanish, either directly, or through their own trusted interpreter

You may not qualify if:

• Patients not diagnosed with LAMA2-CMD
• Patients with no available medical records documenting diagnosis, observation, and treatment between ages 0-5 years
• Patients with medical charts not available in English
• Patients (or Parents of minor patients) not able to consent to participation in English or Spanish, either directly, or through their own trusted interpreter

Sponsors & Collaborators

• Prothelia, Inc.: lead
• Cure CMD: collaborator
• The Bönnemann Laboratory, NINDS, National Institutes of Health: collaborator
• Oscar H Mayer, MD, Children's Hospital of Philadelphia: collaborator
• The Beggs Laboratory, Boston Children's Hospital: collaborator

Study Sites (1)

Cure CMD, Inc.

Lakewood, California, 90712, United States

Location

Related Publications (10)

• Foley AR, Quijano-Roy S, Collins J, Straub V, McCallum M, Deconinck N, Mercuri E, Pane M, D'Amico A, Bertini E, North K, Ryan MM, Richard P, Allamand V, Hicks D, Lamande S, Hu Y, Gualandi F, Auh S, Muntoni F, Bonnemann CG. Natural history of pulmonary function in collagen VI-related myopathies. Brain. 2013 Dec;136(Pt 12):3625-33. doi: 10.1093/brain/awt284. Epub 2013 Nov 22.

  PMID: 24271325 BACKGROUND

• Nadeau A, Kinali M, Main M, Jimenez-Mallebrera C, Aloysius A, Clement E, North B, Manzur AY, Robb SA, Mercuri E, Muntoni F. Natural history of Ullrich congenital muscular dystrophy. Neurology. 2009 Jul 7;73(1):25-31. doi: 10.1212/WNL.0b013e3181aae851.

  PMID: 19564581 BACKGROUND

• Ditaranto R, Boriani G, Biffi M, Lorenzini M, Graziosi M, Ziacchi M, Pasquale F, Vitale G, Berardini A, Rinaldi R, Lattanzi G, Potena L, Martin Suarez S, Bacchi Reggiani ML, Rapezzi C, Biagini E. Differences in cardiac phenotype and natural history of laminopathies with and without neuromuscular onset. Orphanet J Rare Dis. 2019 Nov 19;14(1):263. doi: 10.1186/s13023-019-1245-8.

  PMID: 31744510 BACKGROUND

• Durbeej M. Laminin-alpha2 Chain-Deficient Congenital Muscular Dystrophy: Pathophysiology and Development of Treatment. Curr Top Membr. 2015;76:31-60. doi: 10.1016/bs.ctm.2015.05.002.

  PMID: 26610911 BACKGROUND

• Jain MS, Meilleur K, Kim E, Norato G, Waite M, Nelson L, McGuire M, Duong T, Keller K, Lott DJ, Glanzman A, Rose K, Main M, Fiorini C, Chrismer I, Linton M, Punjabi M, Elliott J, Tounkara F, Vasavada R, Logaraj R, Winkert J, Donkervoort S, Leach M, Dastgir J, Hynan L, Nichols C, Hartnett E, Averion GM, Collins JC, Kim ES, Kokkinis A, Schindler A, Zukosky K, Fee R, Hinton V, Mohassel P, Bharucha-Goebel D, Vuillerot C, McGraw P, Barton M, Fontana J, Rutkowski A, Foley AR, Bonnemann CG. Longitudinal changes in clinical outcome measures in COL6-related dystrophies and LAMA2-related dystrophies. Neurology. 2019 Nov 19;93(21):e1932-e1943. doi: 10.1212/WNL.0000000000008517. Epub 2019 Oct 25.

  PMID: 31653707 BACKGROUND

• Bendixen RM, Butrum J, Jain MS, Parks R, Hodsdon B, Nichols C, Hsia M, Nelson L, Keller KC, McGuire M, Elliott JS, Linton MM, Arveson IC, Tounkara F, Vasavada R, Harnett E, Punjabi M, Donkervoort S, Dastgir J, Leach ME, Rutkowski A, Waite M, Collins J, Bonnemann CG, Meilleur KG. Upper extremity outcome measures for collagen VI-related myopathy and LAMA2-related muscular dystrophy. Neuromuscul Disord. 2017 Mar;27(3):278-285. doi: 10.1016/j.nmd.2016.11.017. Epub 2016 Dec 5.

  PMID: 28087121 BACKGROUND

• Fauroux B, Amaddeo A, Quijano-Roy S, Barnerias C, Desguerre I, Khirani S. Respiratory insight to congenital muscular dystrophies and congenital myopathies and its relation to clinical trial. Neuromuscul Disord. 2018 Sep;28(9):731-740. doi: 10.1016/j.nmd.2018.06.013. Epub 2018 Jul 1.

  PMID: 30097248 BACKGROUND

• Wicklund MP. Rare disease clinical trials: Power in numbers. Neurol Genet. 2016 Aug 4;2(4):e92. doi: 10.1212/NXG.0000000000000092. eCollection 2016 Aug.

  PMID: 27540592 BACKGROUND

• Butterfield RJ. Congenital Muscular Dystrophy and Congenital Myopathy. Continuum (Minneap Minn). 2019 Dec;25(6):1640-1661. doi: 10.1212/CON.0000000000000792.

  PMID: 31794464 RESULT

• Meilleur KG, Jain MS, Hynan LS, Shieh CY, Kim E, Waite M, McGuire M, Fiorini C, Glanzman AM, Main M, Rose K, Duong T, Bendixen R, Linton MM, Arveson IC, Nichols C, Yang K, Fischbeck KH, Wagner KR, North K, Mankodi A, Grunseich C, Hartnett EJ, Smith M, Donkervoort S, Schindler A, Kokkinis A, Leach M, Foley AR, Collins J, Muntoni F, Rutkowski A, Bonnemann CG. Results of a two-year pilot study of clinical outcome measures in collagen VI- and laminin alpha2-related congenital muscular dystrophies. Neuromuscul Disord. 2015 Jan;25(1):43-54. doi: 10.1016/j.nmd.2014.09.010. Epub 2014 Sep 28.

  PMID: 25307854 RESULT

MeSH Terms

Conditions

Muscular dystrophy congenital, merosin negative

Study Officials

• Carsten Bönnemann, MD

  NINDS/NIH

  STUDY DIRECTOR

• Reghan Foley, MD

  NINDS/NIH

  STUDY DIRECTOR

• Oscar H Mayer, MD

  Children's Hospital of Philadelphia

  STUDY DIRECTOR

• Alan Beggs, PhD

  Boston Children's Hospital

  STUDY DIRECTOR

• Gustavo Dziewczapolski, PhD

  Cure CMD

  PRINCIPAL INVESTIGATOR

• Rachel Alvarez, BS

  Cure CMD

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2020
• First Posted: March 6, 2020
• Study Start: April 24, 2020
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2021
• Last Updated: February 7, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Available indefinitely through publication in approximately 18 months (August 2021)
• Access Criteria: Journal will have free access through PubMed

Locations

US (1)