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

January 21, 2022 updated by: Prothelia, Inc.

LAMA2 Retrospective Review of Medical Charts in Infants & Toddlers With LAMA2-Congenital Muscular Dystrophy

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.

Study Overview

Status

Completed

Conditions

Detailed Description

LAMA2-related congenital muscular dystrophy (LAMA2-CMD) is caused by a deficiency of the α2 subunit of laminin due to mutation of the LAMA2 gene.

Typical LAMA2-CMD cases present with prominent hypotonia and weakness in infancy. Congenital contractures are a common finding in the hands and feet. Weakness and contractures are slowly progressive, and most patients do not achieve independent ambulation. Facial weakness and jaw contractures disrupt normal feeding, resulting in failure to thrive. Most patients require nutrition support at an early age. Cardiac involvement is rare. In addition to neuromuscular aspects of the disorder, patients with LAMA2-CMD have central nervous system findings including prominent T2 and fluid-attenuated inversion recovery (FLAIR) abnormalities in the white matter on brain MRI. Despite the prominent changes on MRI, cognitive function is normal, although patients are at risk of seizures, which are seen in 30% of patients.

A number of potential therapies are currently in development for LAMA2-CMD. A larger prospective natural history was conducted at the National Institutes of Health in LAMA2-CMD patients, ages 5-16 years of age, testing and validating a wide variety of outcome measures suitable for use in clinical trials. However, appropriate clinical outcome measures in younger patients (ages 0-5 years) have yet to be validated.

Some treatments currently in development will almost certainly be more effective the earlier the treatment is administered. Given that there is a distinct lack of data for affected individuals less than 6 years of age, this study will be instrumental in building outcome measures appropriate in younger patients. In order to obtain regulatory authorization to launch clinical trials in affected individuals less than 6 years of age, a documented natural history for this age group must be demonstrated.

The primary objective of this study is 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.

The secondary objectives of this study include identifying potential prognostic variables of LAMA2-CMD, identifying adverse events associated with LAMA2-CMD that warrant monitoring and potential preventative measures, and to grow the knowledge base of care standards and optimization to improve the patient's quality of life.

Study Type

Observational

Enrollment (Actual)

75

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Lakewood, California, United States, 90712
        • Cure CMD, Inc.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years to 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Infants and toddlers affected by LAMA2-CMD

Description

Inclusion Criteria:

  1. Patients diagnosed with LAMA2-CMD through:

    1. genetic confirmation of two (2) pathogenic mutations in LAMA2 -OR-
    2. 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)
  2. Patients may be living or deceased
  3. Patients may be male or female
  4. 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.
  5. Patients with medical charts available in English
  6. 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
  7. 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

Exclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Retrospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To characterize the natural history of LAMA2-CMD
Time Frame: Birth to 5 years of age
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
To identify potential prognostic variables of LAMA2-CMD
Time Frame: Birth to 5 years of age
Overall analysis
Birth to 5 years of age
To identify disease symptoms associated with LAMA2-CMD that warrant monitoring and potential preventative measures
Time Frame: Birth to 5 years of age
Overall analysis
Birth to 5 years of age

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Prothelia, Inc.

Collaborators

Cure CMD
The Bönnemann Laboratory, NINDS, National Institutes of Health
Oscar H Mayer, MD, Children's Hospital of Philadelphia
The Beggs Laboratory, Boston Children's Hospital

Investigators

  • Study Director: 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
  • Principal Investigator: Gustavo Dziewczapolski, PhD, Cure CMD
  • Study Director: Rachel Alvarez, BS, Cure CMD

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 24, 2020

Primary Completion (Actual)

December 31, 2021

Study Completion (Actual)

December 31, 2021

Study Registration Dates

First Submitted

March 2, 2020

First Submitted That Met QC Criteria

March 5, 2020

First Posted (Actual)

March 6, 2020

Study Record Updates

Last Update Posted (Actual)

February 7, 2022

Last Update Submitted That Met QC Criteria

January 21, 2022

Last Verified

January 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PRO-LAMA2-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Data will shared in a peer-reviewed publication. De-identified data will be used to inform future studies.

IPD Sharing Time Frame

Available indefinitely through publication in approximately 18 months (August 2021)

IPD Sharing Access Criteria

Journal will have free access through PubMed

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Informed Consent Form (ICF)
  • Clinical Study Report (CSR)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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