Muscle Diseases Clinical Trials Roundtable Summary

Tuesday, December 8, 2009

NIH Campus, Building 40, Conference Room 1201/1203
Bethesda, Maryland

Stephen I. Katz, MD, PhD, NIAMS
Robert H. Carter, MD, NIAMS
Joan McGowan, PhD, NIAMS


This roundtable was convened as part of a larger NIAMS effort to assess its support of clinical trials across the Institute’s mission areas. Goals include identifying needs and opportunities, as well as finding key steps for evaluating trials and the significance of individual studies in the broader context of future clinical needs. There were prior discussions on the subject at the 2009 NIAMS Scientific Retreat and with the NIAMS Advisory Council. A Council subcommittee is being created for further developments. Roundtable attendees canvassed their relevant communities in advance, to bring more than their own opinions to the meeting.


Participants spoke generally about the need to build the knowledge base in an effort to provide the foundation for future translational and clinical research. Most acknowledged that a greater fundamental understanding of healthy and diseased muscle biology is required. There have been significant advances in the pathophysiology of rare muscle diseases, such as some of the muscular dystrophies. However, investigations into more common muscle conditions and symptoms, for example, the mechanisms of pain and fatigue, as well as those involved in muscle atrophy due to aging, could potentially lend insights that would advance treatments for both common and rare diseases. Furthermore, research into the impact of exercise and nutrition could lead to preventive or therapeutic strategies. Identification of biomarkers for disease and co-morbidities were also mentioned.

Even in those diseases or conditions where interventions have been proposed or are being tested, further investigation is needed for continued development. It was pointed out, however, that interventions that exhibit efficacy in animal models often fail in clinical trials, which reinforces the rationale for a greater understanding of human muscle biology. Among the efforts mentioned as current or future needs, the following were discussed as areas of interest:

  • Stimulation of muscle regeneration
  • Inhibition of fibrosis
  • Inhibition of necrosis or apoptosis
  • Promotion of strength
  • Evaluation of genetic and/or environmental determinants


Among the group present, there was great enthusiasm for natural history studies. As the field proceeds with translational studies on many promising therapeutic strategies, it is well-recognized that a better understanding of the clinical features of muscle disease can lead to the design of more effective clinical trials. Such observational studies are especially needed to refine and validate effective biomarkers and other clinical outcome measures. Future genotyping efforts would also benefit from the characterization of cohorts across various diseases. Furthermore, the usefulness of sharing the data produced by unsuccessful and unpublished trials was discussed.

Also of interest was the opportunity and challenge of standardizing treatment protocols and outcome measures across all muscle diseases, and the establishment of a registry to document and track them. Because so many muscle diseases are rare, sharing this information could accelerate the production of data-driven treatments fueled by improved diagnostics and outcome measures.

As clinical trials in muscle diseases progress, the number of well-qualified investigators to carry out the studies may become rate limiting. In order to best leverage the scientific and clinical opportunities in the field, roundtable participants identified the need for greater awareness and education of the public, an enhancement of clinical training on muscle diseases for researchers, and the attraction of new investigators. Such efforts could lead to more accurate diagnoses and the opportunity for earlier intervention, when treatments become available.


The potential high impact and the high cost of clinical trials leads to an increased importance on prioritization strategies. Throughout the day, three similar approaches were embraced and discussed.

First, it was suggested that the Institute organize regular multi-disciplinary meetings, consisting of clinical trial researchers, along with basic and translational scientists, to consider the “readiness” of interventions for clinical trials. These meetings would serve to inform the Institute, but also provide opportunities to generate new ideas and collaborations. The research community could also be encouraged to focus on the most promising therapeutic strategies. It was envisioned that these meetings could generate broad strategies and promote the exchange of information between researchers and patients, across both rare and common diseases.

Another suggestion was to combine or support the collaboration of existing networks. Such communication and collaboration of clinical investigators would help to prioritize scientific opportunities, enhance mentoring, and ensure that an breakthrough in one disease area leads to leveraged advances in others.

Lastly, a plan was considered where clinical trial ideas would be nominated by the community and selected by the Institute to be developed into funding opportunities. The roundtable participants acknowledged that some investigators would be wary of volunteering their best ideas, but felt that the originator would always have an advantage during the review process. The group also debated the process by which nominated ideas would be selected for development.


Participants acknowledged that, when applications for grants to support clinical trials are reviewed in study sections alongside those for basic research studies, the clinical applications may be disadvantaged. This concern stems from the belief that study sections tend to have more limited expertise in clinical research than in basic research. In addition, the recent emphasis on innovation in the review and funding process may be a hurdle for clinical research applications, which may be significant and well-designed, but must limit innovation in order to protect human subjects.

The Clinical and Translational Science Awards (CTSAs) have been a good step forward, providing basic infrastructure through shared resources and staff. They also allow for collaboration and a way to recruit new investigators, but it was felt that they are not a wholesale solution to all clinical needs.

One suggestion was the creation of standing advisory committees dedicated to clinical research in particular tissue or disease areas relevant to the Institute’s mission. These committees could help:

  • Bring various disciplines, ideas, and opportunities together by enhancing communication across disciplines
  • Identify needed infrastructure
  • Advise and mentor applicants and grantees
  • Survey stakeholders qualitatively and quantitatively
  • Provide prioritization and expert advice

The group discussed several different roles in which these committees could interact with the Institute. Also, it was noted that the selection of committee members and the distribution of committees across the Institute’s portfolio would be a significant challenge.

Meeting Participants

BÖNNEMANN, Carsten, M.D.
Assistant Professor, Children’s Hospital of Philadelphia
Abramson Research Center

BOYCE, Amanda, Ph.D.
Director, Muscle Development and Physiology Program
Division of Musculoskeletal Diseases

Co-Director, The Johns Hopkins Myositis Center
Johns Hopkins University

COHN, Ron, M.D.
Assistant Professor, McKusik-Nathans Institute of Genetic Medicine
Johns Hopkins University

CWIK, Valerie, M.D.
Medical Director and Vice President for Research
Muscular Dystrophy Association

DAY, John, M.D., Ph.D.
Director, Paul and Sheila Wellstone Muscular Dystrophy Center
University of Minnesota

GRIGGS, Robert, M.D.
Professor, Department of Neurology
University of Rochester Medical Center

HINTON, Veronica, Ph.D.
Associate Professor of Clinical Neuropsychology
Columbia University College of Physicians and Surgeons

HOFFMAN, Eric, Ph.D.
Director, Center for Genetic Medicine Research
Children’s National Medical Center

MATHEWS, Kathy, M.D.
Director, Division of Pediatric Neurology
University of Iowa Children’s Hospital

MENDELL, Jerry, M.D.
Director, Center for Gene Therapy
Research Institute at Nationwide Children's Hospital and the Ohio State University

MOEN, Laura, Ph.D.
Director, Division of Extramural Research Activities

Director, Muscle Disorders and Therapies Program
Division of Musculoskeletal Diseases

PLOTZ, Paul, M.D.
Chief, Arthritis and Rheumatism Branch
NIAMS Intramural Research Program

Director, Division of Skin and Rheumatic Diseases

STEPHENSON, Bradley, M.A., J.D.
Patient Advocate
San Antonio, TX

WAGNER, Kathryn, M.D., Ph.D.
Director, Center for Genetic Muscle Disorders
The Kennedy Krieger Institute