Clinical Trial: Study of Resting and Exercising Body Functioning in Freeman-Sheldon Syndrome and Related Conditions

Study Status: Completed
Recruit Status: Unknown status
Study Type: Observational

Official Title: Freeman-Sheldon Syndrome Evaluation and Diagnosis in Clinical Settings (FSS-EDICT) I: a Case-Control, Cross-Sectional Study of Baseline and Stress Physiology Parameters

Brief Summary: The hypotheses of the present study of Freeman-Sheldon syndrome (FSS) and related conditions are: (1) that exercise capacity is lower in FSS patients versus normal controls, and the lower exercise capacity is due to changes in the muscles' normal structure and an inability of sufficient quantity of the energy molecule to bind to muscle; (2) this muscle problem reduces amount of air that can get in the lung and amount of oxygen carried in the blood, which then has the effect of increasing heart and respiration rates, blood pressure, and deep body temperature, and produces muscle rigidity; (3) the events noted above, when they occur during cardiac stress testing, are related to a problem similar to malignant hyperthermia (MH) reported in some muscle disorders without use of drugs known to cause MH. MH (a life-threatening metabolic reaction that classically is triggered when susceptible persons receive certain drugs used in anaesthesia.

Detailed Summary:

This study is a research project initiated by the graduate research student (Mikaela I. Poling) and assisted by the clinical genetics fellow and graduate student (Andrés Morales) in partial fulfilment the requirements for their Masters degrees in Clinical and Applied Physiology, under approval, direction, and supervision of the study PI (Rodger J. McCormick).

Importance of Present Study:

FSS is a rare human neuromusculoskeletal disorder present before birth, involving primarily limb and craniofacial deformities. There are no prospective studies addressing physiological parameters, which are necessary to enable understanding of the underlying pathology and pathophysiology of Freeman-Sheldon syndrome. Elucidating any deviations in baseline and stress physiological parameters in FSS patients versus standard normal values and normal control subjects is of critical importance in tailoring therapeutic interventions to this challenging patient population.

Background:

Vanek et al. (1986) purposed FSS spectrum is a non-progressive congenital myopathy, giving pathological and electromyographical (EMG) evidence. They found white fibrose tissue within histologically normal muscle fibres, resulting in abnormal EMGs.

Toydemir et al. (2006) showed that mutations in embryonic myosin heavy chain 3 (MYH3), caused classic FSS phenotype, in which they screened 28 probands. In 20 patients, new missense mutations caused substitution of arginine at position 672 (arg672) by histidine or cytosine; arg672 is found in all myosin proteins post-embryonically. Of the remaining six patients in whom mutations were found, three had new missense or familial mutations; three other patients with sporadic e
Sponsor: Freeman-Sheldon Research Group, Inc.

Current Primary Outcome:

  • Heart rate [ Time Frame: Evaluated at rest and while exercising, during two study visits (lasting an average of 1-3 hours) ]
    Increased heart rate, measured electrocardiographically, is used as an index of cardiovascular strain imposed by needs during exercise and exaggerated by Freeman-Sheldon and related conditions.
  • Oxygen Consumption [ Time Frame: Evaluated at rest and while exercising, during two study visits (lasting an average of 1-3 hours) ]
    Oxygen consumption, measured by ventilation of expired oxygen, is used as a measure of physiological strain imposed by metabolic needs during exercise and exaggerated by Freeman-Sheldon and related conditions.


Original Primary Outcome: Heart rate [ Time Frame: Evaluated during two study visits, lasting an average of 1-3 hours ]

Increased heart rate is used as an index of cardiovascular strain.


Current Secondary Outcome:

  • Non-Invasive Arterial Blood Pressure [ Time Frame: Evaluated at rest and while exercising, during two study visits (lasting an average of 1-3 hours) ]
    Increased non-invasive arterial blood pressure rate is used as an index of cardiovascular strain imposed by needs during exercise and exaggerated by Freeman-Sheldon and related conditions.
  • Spirometry (Forced Expiratory Volume/Forced Vital Capacity) [ Time Frame: Evaluated before and after exercise, during two study visits (lasting an average of 1-3 hours) ]
    Decreased ability of the lungs to move air, measured by forced expiration, is used as an index of strain imposed by Freeman-Sheldon syndrome and related conditions.
  • Saturation of Peripheral Oxygen [ Time Frame: Evaluated at rest and while exercising, during two study visits (lasting an average of 1-3 hours) ]
    Decreased saturation of peripheral oxygen, measured by pulse oxymetry, is used as a measure of physiological strain imposed by metabolic needs during exercise and exaggerated by Freeman-Sheldon and related conditions.
  • Respiratory Rate [ Time Frame: Evaluated at rest and while exercising, during two study visits (lasting an average of 1-3 hours) ]
    Increased respiratory rate, measured by plethysmograph, is used as a measure of physiological strain imposed by metabolic needs during exercise and exaggerated by Freeman-Sheldon and related conditions.
  • Heart Rhythm [ Time Frame: Evaluated at rest and while exercising, during two study visits (lasting an average of 1-3 hours) ]
    Heart rhythms, monitored by electrocardiograph, are used as an index of cardiovascular strain imposed by needs during exercise and exaggerated by Freeman-Sheldon and related conditions.
  • Core Temperature [ Time Frame: Evaluated at rest and while exercising, during two study visits (lasting an average of 1-3 hours) ]
    Increased core temperature, measured as oesophageal temperature, is used as a measure of physiological strain imposed by metabolic needs during exercise and exaggerated by Freeman-Sheldon, related conditions, and malignant hyperthermia.
  • Adenosine Triphosphate [ Time Frame: Evaluated at rest and while exercising, during two study visits (lasting an average of 1-3 hours) ]
    Decreased adenosine triphosphate, measured as capillary blood level, is used as a measure of physiological strain imposed by metabolic needs during exercise and exaggerated by Freeman-Sheldon and related conditions.
  • Perceived Exertion [ Time Frame: Evaluated at rest and while exercising, during two study visits (lasting an average of 1-3 hours) ]
    Increased perceived exertion, measured using the Borg scale, are used as an index of fatigue.
  • Muscle Rigidity [ Time Frame: Evaluated while exercising, during second of two study visits (lasting an average of 1-3 hours) ]
    Increased muscle rigidity, evaluated by clinical examination and patient self-report, is used as an indicator of malignant hyperthermia, when increased core temperature, heart rate, and respiratory rate are present.
  • Functional and Health-Related Quality of Life [ Time Frame: Evaluated in first of two study visits, lasting an average of 1-3 hours ]
    Functional and health-related quality of life, measured with the Medical Outcomes Trust Short Form (36) Health Survey (SF-36), is used as a general prediction of expected physical exercise capacity.
  • Lactic Acid [ Time Frame: Evaluated at rest and while exercising, during two study visits (lasting an average of 1-3 hours) ]
    Lactic acid, measured by capillary blood level, is used as a measure of physiological strain imposed by metabolic needs during exercise and exaggerated by Freeman-Sheldon and related conditions.
  • Glucose [ Time Frame: Evaluated at rest and while exercising, during two study visits (lasting an average of 1-3 hours) ]
    Glucose, measured by capillary blood level, is used as an index of physiological strain, together with lactic acid and adenosine triphosphate capillary blood levels, imposed by metabolic needs during exercise and exaggerated by Freeman-Sheldon and related conditions.


Original Secondary Outcome:

  • Non-Invasive Arterial Blood Pressure [ Time Frame: Evaluated during two study visits, lasting an average of 1-3 hours ]
    Increased non-invasive arterial blood pressure rate is used as an index of cardiovascular strain.
  • Lung Volumes [ Time Frame: Evaluated during two study visits, lasting an average of 1-3 hours ]
    Decreased lung volumes are used as an index of strain caused by Freeman-Sheldon syndrome and related conditions.
  • Saturation of Peripheral Oxygen [ Time Frame: Evaluated during two study visits, lasting an average of 1-3 hours ]
    Decreased saturation of peripheral oxygen is used as an index of strain caused by Freeman-Sheldon syndrome and related conditions.
  • Respiratory Rate [ Time Frame: Evaluated during two study visits, lasting an average of 1-3 hours ]
    Increased respiratory rate is used as an index of cardiovascular strain.
  • Electrocardiogram Tracings [ Time Frame: Evaluated during two study visits, lasting an average of 1-3 hours ]
    Electrocardiogram tracings are used as an index of cardiovascular strain.
  • Oesophageal (Core) Temperature [ Time Frame: Evaluated at rest and while exercising, during second of two study visits (lasting an average of 1-3 hours) ]
    Increased oesophageal (core) temperature is used as an index of cardiovascular strain.
  • Adenosine Triphosphate Blood Levels [ Time Frame: Evaluated at rest and while exercising, during second of two study visits (lasting an average of 1-3 hours) ]
    Adenosine triphosphate blood levels are used as an index of strain caused by Freeman-Sheldon syndrome and related conditions.
  • Borg Scale Ratings of Perceived Exertion [ Time Frame: Evaluated while exercising, during second of two study visits (lasting an average of 1-3 hours) ]
    Increased Borg scale ratings of perceived exertion are used as an index of fatigue.
  • Muscle Rigidity [ Time Frame: Evaluated while exercising, during second of two study visits (lasting an average of 1-3 hours) ]
    Increased Muscle rigidity is used as an indicator of malignant hyperthermia, when increased core temperature, heart, and respiratory rate are present.
  • Medical Outcomes Trust Short Form (36) Health Survey (SF-36) [ Time Frame: Evaluated in first of two study visits, lasting an average of 1-3 hours ]
    Medical Outcomes Trust Short Form (36) Health Survey (SF-36) will be used to assess physical quality of life, which correlates strongly with physical exercise capacity.


Information By: Freeman-Sheldon Research Group, Inc.

Dates:
Date Received: February 26, 2011
Date Started: February 2011
Date Completion:
Last Updated: October 14, 2014
Last Verified: October 2014