Study of Resting and Exercising Body Functioning in Freeman-Sheldon Syndrome and Related Conditions
NCT ID: NCT01306994
Last Updated: 2022-06-06
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
WITHDRAWN
OBSERVATIONAL
2014-03-31
2022-06-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Observing the Effect of Fascial Manipulation in Athletes With Shin Splits.Tibial Stress Syndrome.
NCT03198260
CSS-Assessing the Course of Degenerative Cervical Spinal Stenosis Using Functional Outcomes
NCT04381663
The Effect of Spinal Manipulation on Hip Extension Strength and Jump Height
NCT05689723
Effects of Comprehensive Correcting Exercise Program and Mckenzie Exercises in Patients With Sternosymphyseal Syndrome
NCT06751771
Effects of Osteopathic Manipulative Treatment of Fascial Restrictions on Body Awareness, Mood, and Proprioception
NCT04945798
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
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 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.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
CASE_CONTROL
CROSS_SECTIONAL
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Syndrome Group
Individuals with Freeman-Sheldon, Sheldon-Hall, distal arthrogryposis type 1, or distal arthrogryposis type 3
Lactate, Glucose, and Adenosine Triphosphate Blood Levels
Completed during the clinical examination and exercise test by the researchers, lactate, glucose, and free and total adenosine triphosphate blood levels are determined at rest and during exercise.
Physiological Stress Test
During exercise, heart and lung function are monitored for changes caused by exercise, which increases the body's need for oxygen and puts extra demands on the heart. In this study, testing is done using a cycle ergometer and conducted according to the standardised exponential exercise protocol (STEEP).
Functional Enquiry Form
Evaluated before clinical examination, it is a checklist of medical problems.
Strength, Joint ROM, Girth and Length Measurements
Completed during the clinical examination by the researchers, it is a structured approach to evaluation of muscles, joints, arms, thighs, and legs.
Study Physical Examination
Completed during the clinical examination by the researchers, it is a structured approach to a full physical examination (minus breasts, genitalia, or rectum).
Observational Gait Analysis
Completed during the clinical examination by researchers, it is a structured approach to evaluation of a person's walking.
Mental Health Interview
Completed during the clinical examination by the researchers, it is a general evaluation of mental health status.
Control Group
Healthy individuals
Lactate, Glucose, and Adenosine Triphosphate Blood Levels
Completed during the clinical examination and exercise test by the researchers, lactate, glucose, and free and total adenosine triphosphate blood levels are determined at rest and during exercise.
Physiological Stress Test
During exercise, heart and lung function are monitored for changes caused by exercise, which increases the body's need for oxygen and puts extra demands on the heart. In this study, testing is done using a cycle ergometer and conducted according to the standardised exponential exercise protocol (STEEP).
Functional Enquiry Form
Evaluated before clinical examination, it is a checklist of medical problems.
Strength, Joint ROM, Girth and Length Measurements
Completed during the clinical examination by the researchers, it is a structured approach to evaluation of muscles, joints, arms, thighs, and legs.
Study Physical Examination
Completed during the clinical examination by the researchers, it is a structured approach to a full physical examination (minus breasts, genitalia, or rectum).
Observational Gait Analysis
Completed during the clinical examination by researchers, it is a structured approach to evaluation of a person's walking.
Mental Health Interview
Completed during the clinical examination by the researchers, it is a general evaluation of mental health status.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Lactate, Glucose, and Adenosine Triphosphate Blood Levels
Completed during the clinical examination and exercise test by the researchers, lactate, glucose, and free and total adenosine triphosphate blood levels are determined at rest and during exercise.
Physiological Stress Test
During exercise, heart and lung function are monitored for changes caused by exercise, which increases the body's need for oxygen and puts extra demands on the heart. In this study, testing is done using a cycle ergometer and conducted according to the standardised exponential exercise protocol (STEEP).
Functional Enquiry Form
Evaluated before clinical examination, it is a checklist of medical problems.
Strength, Joint ROM, Girth and Length Measurements
Completed during the clinical examination by the researchers, it is a structured approach to evaluation of muscles, joints, arms, thighs, and legs.
Study Physical Examination
Completed during the clinical examination by the researchers, it is a structured approach to a full physical examination (minus breasts, genitalia, or rectum).
Observational Gait Analysis
Completed during the clinical examination by researchers, it is a structured approach to evaluation of a person's walking.
Mental Health Interview
Completed during the clinical examination by the researchers, it is a general evaluation of mental health status.
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Sheldon-Hall syndrome,
* Distal arthrogryposis type 1, or
* Distal arthrogryposis type 3
* Deceased patients with enough clinical information available to satisfy study requirements
* Subjects must be healthy and free of active disease.
* Subject or parent of minor child must be willing to give consent.
* Subjects must fall within the age-bracket to be matched with a Syndrome Group patient already screened and enroled in the study
* Subjects must be non-tobacco users and non-drinkers.
Exclusion Criteria
* Deceased patients without enough clinical information available to satisfy study requirements
* Patients with other anomalies, not having one of the above syndromes
* Patients or parents of minor children not willing to give consent
* Mature female patients who are pregnant or breast-feeding will be reassessed for consideration for enrolment.
* Mature female patients who are currently experiencing menses will be reassessed for consideration for enrolment.
* Patients with active, acute comorbid illness will be reassessed for consideration for enrolment.
* Subjects exceptional for their age in body weight, stature, or habitus according to commonly accepted guidelines
* Subjects with active psychiatric illness, as manifested by abnormal mental status examination
* Subjects with active physical illness, especially respiratory or cardiac problem, as manifested by abnormal findings on physical examination
* Subjects with significant diagnosis of a constitutional disease or genetic disorder
* Subjects with a history of severe trauma resulting in either an anatomical of physiological deformity that impairs function
* Non-living subjects
* Candidates who fail the stress test
* Mature female subjects who are pregnant or breast-feeding will be reassessed for consideration for enrolment.
* Mature female subjects who are currently experiencing menses will be reassessed for consideration for enrolment.
* Subjects with active, acute illness will be reassessed for consideration for enrolment.
* Any other condition or anomaly expected to affect current physiology listed in AFI-48-123.
ALL
Yes
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Freeman-Sheldon Research Group, Inc.
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Freeman-Sheldon Research Group, Inc. Headquarters
Buckhannon, West Virginia, United States
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Vanek J, Janda J, Amblerova V, Losan F. Freeman-Sheldon syndrome: a disorder of congenital myopathic origin? J Med Genet. 1986 Jun;23(3):231-6. doi: 10.1136/jmg.23.3.231.
Toydemir RM, Rutherford A, Whitby FG, Jorde LB, Carey JC, Bamshad MJ. Mutations in embryonic myosin heavy chain (MYH3) cause Freeman-Sheldon syndrome and Sheldon-Hall syndrome. Nat Genet. 2006 May;38(5):561-5. doi: 10.1038/ng1775. Epub 2006 Apr 16.
Stevenson DA, Carey JC, Palumbos J, Rutherford A, Dolcourt J, Bamshad MJ. Clinical characteristics and natural history of Freeman-Sheldon syndrome. Pediatrics. 2006 Mar;117(3):754-62. doi: 10.1542/peds.2005-1219.
Portillo AL, Chamberlain RL, McCormick RJ, Poling MI. Histopathological and Operative Findings in a Severe Case of Freeman-Sheldon Syndrome: Implications for Nosology and Therapy. (Unpubl.) 2010.
Litman RS, Rosenberg H. Malignant hyperthermia: update on susceptibility testing. JAMA. 2005 Jun 15;293(23):2918-24. doi: 10.1001/jama.293.23.2918.
McCormick RJ. A Proposal for a Thesis: Heat Tolerance in Exercising Lean and Obese Middle-Aged Men. DEd diss., the Pennsylvania State University, 1973.
Myhill S, Booth NE, McLaren-Howard J. Chronic fatigue syndrome and mitochondrial dysfunction. Int J Clin Exp Med. 2009;2(1):1-16. Epub 2009 Jan 15.
Northridge DB, Grant S, Ford I, Christie J, McLenachan J, Connelly D, McMurray J, Ray S, Henderson E, Dargie HJ. Novel exercise protocol suitable for use on a treadmill or a bicycle ergometer. Br Heart J. 1990 Nov;64(5):313-6. doi: 10.1136/hrt.64.5.313.
Franklin B, Fern A, Fowler A, Spring T, Dejong A. Exercise physiologist's role in clinical practice. Br J Sports Med. 2009 Feb;43(2):93-8. doi: 10.1136/bjsm.2008.055202. Epub 2008 Dec 2.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
U1111-1120-5931
Identifier Type: OTHER
Identifier Source: secondary_id
000079
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.