Study of Resting and Exercising Body Functioning in Freeman-Sheldon Syndrome and Related Conditions (FSS-EDICT I)
|First Received Date ICMJE||February 26, 2011|
|Last Updated Date||October 22, 2013|
|Start Date ICMJE||February 2011|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||Heart rate [ Time Frame: Evaluated during two study visits, lasting an average of 1-3 hours ] [ Designated as safety issue: Yes ]
Increased heart rate is used as an index of cardiovascular strain.
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT01306994 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Study of Resting and Exercising Body Functioning in Freeman-Sheldon Syndrome and Related Conditions|
|Official Title ICMJE||Freeman-Sheldon Syndrome Evaluation and Diagnosis in Clinical Settings (FSS-EDICT) I: a Case-Control, Cross-Sectional Study of Baseline and Stress Physiology Parameters|
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.
This study is a research project initiated by the research student (Mikaela I. Poling) and assisted by the clinical genetics fellow (Andrés Morales) in partial fulfillment the FSRG Foundation Programme, under approval, direction, and supervision of the study PI (Rodger J. McCormick) and Sub-Investigator (Richard A. Chamberlain).
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.
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 expression had new, which were also found in Sheldon-Hall syndrome (SHS); two patients had no recognized mutations. They postulated these allelic variations at arg672 could affect adenosine triphosphate (ATP) binding. It is unknown how these mutations might correlate to the phenotypes observed. Their laboratory, including Stevenson et al. (2006) also presented strong evidence that FSS and SHS and similar distal arthrogryposes (DA) were distinct entities based on phenotype, natural history, and genotype.
Portillo et al. (unpublished data), in study of biopsies from their patient, found no evidence of muscle in the superior orbicularis oculi and found highly variable fibre size as a single pathological feature in a single vastus lateralis biopsy. Clinically, their patient, who had to-date the most severe expression of FSS, exhibited no function of the superior eyelid and reasonable muscle tone, bulk, and strength in the thigh. These findings suggested variable syndromic affectation by body region. They reported exertional dyspnea and resting tachycardia, without pathological features, in their patient and anecdotal information concerning exertional dyspnea in two other adult FSS patients. They also documented the occurrence of unexplained, seemingly stress-induced, episodic fever in their patient that resembled the malignant hyperthermia (MH) clinical triad of hyperthermia, tachycardia, and muscle rigidity.
In addition to age, gender, physical activity status, and concomitant disease and disability, maximal oxygen uptake, a function of exercise capacity, is genetically-controlled, and as already documented in other muscle disorders, the idiopathic febrile episodes reported by Portillo et al. may share physiological and biochemical similarities to the well-defined congenital muscle anomaly MH, which classically occurs when susceptible individuals receive inhaled anaesthetics, such as ether and halothane, or depolarizing muscle relaxants during surgery. Together, these clinical observations suggested there may be some syndromic relationship to exercise capacity and development of MH-like febrile syndrome, and it will be important to demonstrate these findings in a controlled experimental setting.
Significant differences among the similar distal arthrogryposes (DAs) may exist, with respect to the above, and this will be important to define experimentally, as well. Data concerning baseline and stress physiology in FSS and similar DAs could help to further define the distinct DA phenotypes clinically similar to FSS, contributing to nosological classification of FSS and related entities. This study will include FSS, Sheldon-Hall syndrome, DA type 1, and DA type 3.
|Study Type ICMJE||Observational|
|Study Design ICMJE||Observational Model: Case Control
Time Perspective: Cross-Sectional
|Target Follow-Up Duration||Not Provided|
|Biospecimen||Retention: None Retained
Blood samples will be taken but no retention is expected.
|Sampling Method||Probability Sample|
Patients world-wide are welcome, so-long as they have a qualifying diagnosis. Healthy controls are welcome world-wide, as well.
|Study Group/Cohort (s)||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE||20|
|Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
Syndrome Group Inclusion Criteria:
Syndrome Group Exclusion Criteria:
Control Group Inclusion Criteria:
Control Group Exclusion Criteria:
|Accepts Healthy Volunteers||Yes|
|Location Countries ICMJE||United States, Guatemala|
|NCT Number ICMJE||NCT01306994|
|Other Study ID Numbers ICMJE||000079, U1111-1120-5931|
|Has Data Monitoring Committee||No|
|Responsible Party||Freeman-Sheldon Research Group, Inc.|
|Study Sponsor ICMJE||Freeman-Sheldon Research Group, Inc.|
|Collaborators ICMJE||Not Provided|
|Information Provided By||Freeman-Sheldon Research Group, Inc.|
|Verification Date||October 2013|
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