Welcome

The mission of the Rehabilitation Research and Training Center in Neuromuscular Diseases (RRTC/NMD) at the University of California, Davis is to improve the lives of individuals with neuromuscular diseases by developing and evaluating new strategies that address lifelong needs for evidence-based medical care and counseling, psychosocial well-being, education, and independent living.

NIDRR Rehabilitation Research and Training Center in Neuromuscular Diseases:
Enhancing the Health and Wellness of Individuals with Neuromuscular Diseases

 The purpose of the NIDRR Rehabilitation Research and Training Center in Neuromuscular Diseases (RRTC-NMD) is to enhance the health, wellness, function and quality of lives of individuals with neuromuscular diseases (NMDs). To achieve this purpose, we have proposed the following programmatic goals for the RRTC-NMD 2009-2014:
1) Develop and test improved outcome measures for use in intervention and natural history studies in persons with NMDs;
2) Identify or develop and test the effectiveness of new medical rehabilitation interventions, and document the effectiveness of existing interventions in persons with NMDs;
3) Provide training, including graduate, pre-service, and in-service training, to help rehabilitation personnel effectively provide rehabilitation services to individuals with NMDs;
4) Disseminate informational materials and provide technical assistance to individuals with NMDs, their representatives, providers, and other interested parties; and
5) Serve as a center of national excellence in rehabilitation research for individuals with disabilities, their representatives, providers, and other interested parties.

Recent Projects

Project 1: State-of-the Art Clinical Endpoints versus Person-Reported Outcomes in Individuals with Neuromuscular Disease: Reliability, Validity and Responsiveness to Change. UC Davis Investigators: Jay Han, MD, R. Ted Abresch, MS, Erik Henricson, MS, MPH, and Craig McDonald, MD.
Summary. Clinicians, researchers and industry are in need of better clinical information to evaluate the progress and deterioration of individuals with neuromuscular disorders (NMDs), and to aid in development of new state-of-the-art interventions. To test the efficacy of potential treatments, researchers are in need of validated and responsive outcome measures that demonstrate clinically-meaningful change within the span of Phase II/III clinical trials. Specific Aims Specific Aim 1. Characterize and define the range of clinical severity and disease course of the major neuromuscular diseases (NMDs) a. Use a cross-sectional sample of patients to characterize a clinical profile of the major NMDs. b. Assess whether commonly-used and novel clinical measures show significant age- and disease-severity related relationships and can be used to monitor disease progression. Specific Aim 2. The RRTC/NMD will test state-of-the-art clinical endpoints and person-reported NeuroQOL measures of 1) mobility and motor function; and 2) secondary conditions including pain, fatigue, and respiratory impairments, and sleep disorders through a 1-year observational study of 360 adolescents and adults with NMDs by: a. Conducting a one-year longitudinal assessment to determine the rate of change of selected clinical outcome measures in NMDs for the purpose of clinical trial planning; b. Determining the interrelationship of the outcome measures including NeuroQOL domains, and the degree of change in the identified measures that is clinically meaningful and predictive of disease milestones; c. Assessing the feasibility, test-retest reliability, and validity of the identified measures; and d. Defining clinically-significant differences by testing the responsiveness of the identified measures at different ages and/or stages of disease where patients are known to show improvement, stability or decline when using commonly employed clinical outcome measures in NMD clinical research.
Project 2. Development of a Child Version of the NeuroQOL: Reliability, Validity and Responsiveness to Change in Individuals with Neuromuscular Diseases. UC Davis Investigators: Craig McDonald, MD, R., Erik Henricson, MPH, Ted Abresch, MS, Jay Han, MD Northwestern Investigators: David Cella, Ph.D., David Victorson, Ph.D., Jin-Shei Lai, Ph.D. Summary: The RRTC-NMD will develop and test an improved outcome measure to assess health and rehabilitation outcomes for use with individuals with NMDs. Specifically we will develop and validate a child version of the NIH NeuroQOL – a state of the art person reported outcome measure – for children with NMD ages 5 to 12 and their parents. The sensitivity and responsiveness of this new person reported outcome measure to change due to an intervention will be assessed in the two dimensions of a) improved mobility, and b) prevention or reduction of secondary conditions (e.g., pain, fatigue, muscle weakness, associated sleep disorders). Specific Aims: Aim 1: Develop item pools for a child version of the NeuroQOL for the domains of mobility and secondary conditions (decreased self care, pain and fatigue) for children with NMD ages 5-12 and their parents. Aim 2: Perform bank/scale field testing of child NeuroQOL item parameters in both children and parents. Aim 3: Analyze the psychometric characteristics of banks and scales for the child version of the NeuroQOL. Aim 4: Evaluate the responsiveness to change of the child NeuroQOL items in comparison to the PedsQL Neuromuscular module to change, and the ability to detect short-term improvements by studying a cohort of 5-12 year-old boys with DMD who initiate therapy with corticosteroids, which has been shown to significantly improve strength and motor function over 12-weeks.
Project 3: Evaluation of CDC management guidelines for Duchenne muscular dystrophy through a five-year multinational longitudinal study. UC Davis Investigators: Erik Henricson, MPH, Craig McDonald, MD, R. Ted Abresch, MS, Jay Han, MD Children’s National Medical Center Investigators: Avital Cnaan,Ph.D, Angela Zimmerman, BS Adrienne Arrieta, MS, , Trinh Doung, MS PT, Fengming Hu, MS, Robert Leshner, MD, and the CINRG Investigators Summary. The purpose of this project is to validate and establish new standards of integrated care and optimal interventions for individuals with Duchenne muscular dystrophy (DMD). We have utilized the Cooperative International Neuromuscular Research Group (CINRG) network to develop an RRTC-based “Model Systems Program” approach to assess current treatment and care recommendations and to carry out research and dissemination activities within a large international network. Specific Aims: Using an existing retrospective/prospective cohort study of individuals with Duchenne muscular dystrophy, conduct retrospective-prospective nested case-control and case-cohort analyses to evaluate the effectiveness of preventive interventions identified by the CDC DMD Care Considerations Group as requiring further study. 1. Continue assessments of all 347 participants enrolled in UCD0305: A Cooperative International Neuromuscular Research Group (CINRG) Study of the Relationship Between Impairment, Activity Limitation, Participation and Quality of Life in Persons With Confirmed Dystrophinopathies through five years of follow-up. 2. Using data from the UCD0305 study, develop retrospective-prospective nested case-control studies to: a. Assess the incidence of secondary conditions of DMD and relative risks of developing those conditions based on exposure to preventive interventions. b. Examine the associations between interventions and incidence and severity of secondary conditions, achievement of disease milestones and measures of motor function and mobility.
Project 4: Evaluation of NeuroQOL in non-ambulatory subjects with nonsense-mutation-mediated Duchenne and Becker muscular dystrophy who are treated with PTC124 (ataluren), a novel drug that promotes read-through of premature stop codons in the dystrophin gene. Investigators: Craig McDonald MD, Jay Han MD, Erik Henricson MPH, R. Ted Abresch MS Summary. In continuation of its ongoing partnership with PTC Therapeutics in the testing of the first-in-class drug PTC124 (ataluren), the UC Davis RRTC-NMD will facilitate the development and conduct of an open-label clinical trial of ataluren in thirty non-ambulatory boys with nonsense-mutation-mediated D/BMD who are 12 years or older. There is a lack of consensus regarding the objective measurement of function, and a need to develop additional measures. During the course of the clinical trial, we will conduct a companion study to evaluate the validity and responsiveness to change of the NeuroQOL health-related quality of life assessment in clinical trials in this more severely affected non-ambulatory group. We will also evaluate the relationship of the NeuroQOL total score, activities of daily living / upper extremity function and wheelchair mobility subscales to the clinical trial measures of upper extremity strength, upper extremity function and pulmonary function to determine whether the NeuroQOL assessment reflects subjects’ changes in strength, function and mobility. Specific aims: Aim 1: Participate in a Phase 2a study of ataluren (PTC124) in nonambulatory patients with nonsense-mutation-mediated Duchenne/Becker muscular dystrophy with PTC Therapeutics, Inc. a. Develop training materials and conduct initial and follow-up investigator and clinical evaluator training relating to clinical outcome measures of strength and function employed in the study. b. Participate as a study site in the clinical trial to achieve the following primary and secondary aims: i. Primary - To assess the safety and tolerability of ataluren in nonambulatory subjects with nmDMD/BMD. ii. Secondary - To provide a comprehensive evaluation of the effects of ataluren on major clinical manifestations and on the pathophysiology of the disease, including physical, pulmonary, cardiac and cognitive function, health-related quality of life, and pharmacodynamics, drug compliance, drug exposure, and safety profiles. Aim 2: Evaluate NeuroQOL as a clinical trial outcome measure in non-ambulatory DMD compared to clinical outcome measures from the ataluren clinical trial: In a companion study to the 48-week ataluren clinical trial, investigators will characterize the validity and responsiveness to change of the NeuroQOL health-related quality of life assessment in clinical trials in a non-ambulatory group of boys with DMD at baseline, 24 and 48-week timepoints. Investigators will: a. Determine the rate of change of NeuroQOL and clinical outcome measures in the ataluren clinical trial. b. Determine the interrelationship of the NeuroQOL domains, and whether the degree of change in ataluren-treated clinical outcome measures of upper extremity strength, upper extremity function, pulmonary function, and wheelchair mobility is clinically meaningful and predictive of disease milestones. c. Assess the feasibility, test-retest reliability, and validity of the identified measures in a more severely affected population who use wheelchairs for mobility; d. Define clinically-significant differences by testing the responsiveness of the identified measures at different ages and/or defined stages of disease where patients are known to show improvement, stability or decline when using commonly employed clinical outcome measures in DMD clinical research.

Training Activities

Project Director: Jay J. Han, MD

Vision and Goal: Advancing rehabilitation research in NMDs by recruiting, training, and nurturing the next generation of multidisciplinary clinical researchers.

The proposed training program will be of sufficient quality, intensity, and duration while providing individualized focus in medical rehabilitation and research area specific for each scholar. The training program will closely utilize new fund of knowledge derived from and coordinated with the proposed research activities. In addition, the training materials and methods will be accessible to individuals with disabilities. Continuous evaluation process will be in place to critically assess the progress of the individual scholars as well as the effectiveness of the training program in achieving the stated goals, and remedies implemented.
a. Integration: Education, training, and career development are integral to all RRTC-NMD activities--every program contributes to the educational and training mission.
b. Rigor: Participants and content are selected to optimize the quality of the training.
c. Team Science: The multidisciplinary culture at UC Davis and the education programs of the RRTC-NMD includes approaches and focus on developing skills in team science.
d. Diversity: The RRTC-NMD at UC Davis leadership values and promotes multidisciplinary and racial, ethnic, linguistic, age, disability, and gender diversity in all aspects of our activities. We will collaborate with UC Davis' overall diversity plan.
e. Continuous Evaluation: The RRTC-NMD strives to continually improve its quality of the training programs. Constant monitoring and evaluation are required to ensure success.
f. Research Activities: The proposal brings new innovative training initiatives and builds upon training activities of the previous RRTC-NMD grant cycles. Scholars will be trained in neuromuscular rehabilitation research, standards of care, interventions, new therapies, and outcome measurement that are highly relevant to stakeholders. Training will be provided to diverse target audiences as shown below:


Training Audiences
1. Post-graduate clinician-researchers
a. 3-5 Post-doctoral ACGME Fellows in Neuromuscular Medicine
b. 12 PM&R Residents (3 positions per year for four years)
2. In-service training (NMD researchers, practitioners, industry, allied health personnel)
a. Members of the Cooperative International Neuromuscular Research Group
b. MDA Clinical Research Network and PTC Therapeutics.
3. Pre-service (Undergraduate research assistants, Graduate students, Medical students)


Post-doctoral Fellow in Neuromuscular Medicine. The training program proposes to train 3-5 physiatrists and neurologists in a comprehensive, but individualized 1-2 year ACGME-accredited program in the subspecialty of Neuromuscular Medicine. The purpose is to develop skilled clinician-researchers and PhDs with the specialized and multidisciplinary skills required to become independent researchers that will improve the lives of individuals with NMDs.
Goals:
i. To train 3-5 physiatrists and/or neurologiss in a comprehensive ACGME-accredited program in the subspecialty of Neuromuscular Medicine over the 5-year grant period.
ii. To offer a mentored, competency-based didactic curriculum so scholars can integrate basic, rehabilitative and clinical science knowledge into more effective treatments for NMDs.
iii. Provide oversight of RRTC training to ensure the development of a fully competent multidisciplinary research-oriented rehabilitation investigator who can successfully design and conduct clinical trials evaluating rehabilitative therapies and investigational new agents.


In-service Training (NMD researchers, clinical coordinators, allied health personnel)
During the annual Cooperative International Neuromuscular Research Group scientific meetings, we will conduct an annual one-day training course to 20-40 clinical evaluators to train and evaluate their use of outcome measures in NMDs in the following areas:
Module A: Impairment Outcome Measures in Progressive Neuromuscular Disease Clinical Research. Methodologies relating to the measurement of body composition, strength, fatigue, contractures, spinal deformity, pulmonary impairment, and cardiac impairment.
Module B: Assessment of Functional Limitations, and Participation. Methodologies relating to the assessment of functional limitations in mobility, NIH Toolbox, timed motor performance, physical activity, and participation
Module C: The Role of Exercise and Physical Activity in Neuromuscular Diseases. Adaptations to exercise training in NMDs as compared to able-bodied humans, including adaptations to resistance and aerobic training, exercise-induced muscle damage and role of fatigue.


Separate break-out training sessions conducted for 20-40 clinical coordinators will cover the following topics:
Module A: The Basics of Clinical Research in NMD. Fundamental concepts, trends, regulations, and practices in NMD clinical research. An overview of industry and government practices and policies in the development of patient care products (drugs, devices, biologicals and diagnostics) and treatment protocols. Focus on the regulatory environment, maintaining data, case report Forms (CRFs), audits, ethical and fiscal issues.
Module B: The Processes of Clinical Research. Introduction to the processes, procedures and treatment protocols in the development of patient care products, including RO1 applications, clinical trial protocols, institutional review board standards, adverse event monitoring and the supporting documentation and practices to obtain the FDA approval.
Module C: Measuring quality of life assessment and outcomes for clinical trials in NMDs.

News

Winter 2005 NMDINFO News 03/08/06

Featuring information on Duchenne and Becker Muscular Dystrophies

Link to downloadable PDF version

To view the Table of Contents and browse selected items in the newsletter, see the Table of Contents

Recent Report - National Institutes of Health Action Plan for Muscular Dystrophy 03/08/06

Read about it here.

Anesthesia Use in Neuromuscular Diseases 07/19/05

Anyone having surgery should be aware of the risks associated with the surgical procedure and/or complications that may arise during and/or after it. For patients with neuromuscular diseases (NMD), there are frequently added risks with the use of anesthesia. While the administration of anesthetics to people with NMDs has become safer over the past decade, there are several things people with NMDs should know regarding their care and the potential for increased risk of complications due to the anesthesia. While certain risk factors are increased in people with NMDs who undergo anesthesia, each individual is different and reactions to anesthetics may be different. The following is a brief description of complications that may occur among people with NMDs who have surgery. As with all medical procedures, you should talk to your doctor about the specifics of your case and what you should anticipate. more

Emery- Dreifuss Muscular Dystrophy 05/01/05

Article on involvement of the heart in Emery-Dreifuss muscular dystrophy (Quest, May-June,Vol 12, No 3, 2005).
Link to Article on MDAUSA.org

Research Reports on Duchenne Muscular Dystrophy 03/28/05

Full Article

  1. A report on the use of corticosteroids for treatment of DMD
  2. Genetic engineering in Duchenne muscular dystrophy

Respiratory Care in Duchenne Muscular Dystrophy: Recommendation of the American Thoracic Society 03/28/05

In August 2004 the American Thoracic Society adopted an official statement on the appropriate respiratory care for patients with Duchenne muscular dystrophy (DMD).

The purpose of the statement is to educate the practitioner about new approaches and therapies that are available for the management of the respiratory complications of DMD. Although respiratory disease in DMD is its major cause of morbidity and mortality, there is inadequate awareness of its treatable nature.

More onRespiratory Care

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