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

NCT01306994 | Withdrawn

• 2 other identifiers: 000079U1111-1120-5931
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Arthrogryposis; Craniofacial Abnormalities

Keywords

Exercise Test; Bicycle Ergometry Test; Stress Test

Outcome Measures

Primary Outcomes (2)

• Heart rate

  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.

  Evaluated at rest and while exercising, during two study visits (lasting an average of 1-3 hours)

• Oxygen Consumption

  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.

  Evaluated at rest and while exercising, during two study visits (lasting an average of 1-3 hours)

Secondary Outcomes (12)

• Non-Invasive Arterial Blood Pressure

  Evaluated at rest and while exercising, during two study visits (lasting an average of 1-3 hours)

• Spirometry (Forced Expiratory Volume/Forced Vital Capacity)

  Evaluated before and after exercise, during two study visits (lasting an average of 1-3 hours)

• Saturation of Peripheral Oxygen

  Evaluated at rest and while exercising, during two study visits (lasting an average of 1-3 hours)

• Respiratory Rate

  Evaluated at rest and while exercising, during two study visits (lasting an average of 1-3 hours)

• Heart Rhythm

  Evaluated at rest and while exercising, during two study visits (lasting an average of 1-3 hours)

Other Outcomes (2)

• Body Composition

  Evaluated before exercise, during two study visits (lasting an average of 1-3 hours)

• Hand Grip Strength

  Evaluated during the first of two study visits

Study Arms (2)

Syndrome Group

Individuals with Freeman-Sheldon, Sheldon-Hall, distal arthrogryposis type 1, or distal arthrogryposis type 3

Other: Lactate, Glucose, and Adenosine Triphosphate Blood Levels; Procedure: Physiological Stress Test; Other: Functional Enquiry Form; Other: Strength, Joint ROM, Girth and Length Measurements; Other: Study Physical Examination; Other: Observational Gait Analysis; Other: Mental Health Interview

Control Group

Healthy individuals

Other: Lactate, Glucose, and Adenosine Triphosphate Blood Levels; Procedure: Physiological Stress Test; Other: Functional Enquiry Form; Other: Strength, Joint ROM, Girth and Length Measurements; Other: Study Physical Examination; Other: Observational Gait Analysis; Other: Mental Health Interview

Interventions

Lactate, Glucose, and Adenosine Triphosphate Blood Levels OTHER

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.

Also known as: ATP levels, ATP blood levels, adenosine triphosphate test, blood test for ATP, blood test for adenosine triphosphate, ATP blood test, adenosine triphosphate blood test, ATP test, glucose test, glucose blood test, sugar test, lactic acid levels, lactic acid blood test, lactate blood test, lactate levels

Control Group; Syndrome Group

Physiological Stress Test PROCEDURE

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).

Also known as: stress test, graded exercise test, maximal exercise test, VO2 max test, maximal oxygen uptake test, exercise tolerance test, exercise stress test

Control Group; Syndrome Group

Functional Enquiry Form OTHER

Evaluated before clinical examination, it is a checklist of medical problems.

Also known as: FSRG Form 08, health history, review of systems, systems review, medical history, personal health history

Control Group; Syndrome Group

Strength, Joint ROM, Girth and Length Measurements OTHER

Completed during the clinical examination by the researchers, it is a structured approach to evaluation of muscles, joints, arms, thighs, and legs.

Also known as: SF 527, Standard Form 527, musculoskeletal examination, musculoskeletal exam, musculoskeletal evaluation, musculoskeletal assessment, extremity examination, extremity evaluation, extremity assessment, extremity exam

Control Group; Syndrome Group

Study Physical Examination OTHER

Completed during the clinical examination by the researchers, it is a structured approach to a full physical examination (minus breasts, genitalia, or rectum).

Also known as: FSRG Form 14, physical examination, physical evaluation, physical assessment, medical examination, medical evaluation, medical assessment, full medical examination, full medical evaluation, full medical assessment, periodic medical examination, periodic medical evaluation, periodic medical assessment, annual medical examination, annual medical evaluation, annual medical assessment, yearly medical examination, yearly medical evaluation, yearly medical assessment, full physical examination, full physical evaluation, full physical assessment, complete physical examination, complete physical evaluation, complete physical assessment, yearly physical examination, yearly physical evaluation, yearly physical assessment, annual physical examination, annual physical evaluation, annual physical assessment, periodic physical examination, periodic physical evaluation, periodic physical assessment, screening physical examination, screening physical evaluation, screening physical assessment, screening physical, physical, periodic physical, annual physical, annual check-up, annual check up, yearly physical, yearly check up, yearly check-up, check up, check-up, medical check-up, medical check up, annual medical check-up, annual medical check up, yearly medical check-up, yearly medical check up, periodic medical check-up, periodic medical check up, periodic health evaluation, periodic health assessment, annual health evaluation, annual health assessment, yearly health evaluation, yearly health assessment, screening health evaluation, screening health assessment, screening medical examination, screening medical evaluation, screening medical assessment, med check

Control Group; Syndrome Group

Observational Gait Analysis OTHER

Completed during the clinical examination by researchers, it is a structured approach to evaluation of a person's walking.

Also known as: FSRG 10, gait analysis, functional gait analysis

Control Group; Syndrome Group

Mental Health Interview OTHER

Completed during the clinical examination by the researchers, it is a general evaluation of mental health status.

Also known as: psychiatric examination, psychiatric evaluation, psychiatric assessment, psychiatric interview, diagnostic mental health examination, diagnostic mental health evaluation, diagnostic mental health assessment, diagnostic psychiatric examination, diagnostic psychiatric evaluation, diagnostic psychiatric assessment, diagnostic psychiatric interview, intake examination, intake evaluation, intake assessment, intake interview, mental health evaluation, mental health examination, mental health assessment, psychological examination, psychological evaluation, psychological assessment, psychological interview, psychological intake examination, psychological intake evaluation, psychological intake assessment, psychological intake interview

Control Group; Syndrome Group

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients world-wide are welcome, so-long as they have a qualifying diagnosis. Healthy controls are welcome world-wide, as well.

You may qualify if:

• Freeman-Sheldon syndrome,
• Sheldon-Hall syndrome,
• Distal arthrogryposis type 1, or
• Distal arthrogryposis type 3
• Deceased patients with enough clinical information available to satisfy study requirements

You may not qualify if:

• Individuals not confirmed to have a condition under study
• 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 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.
• 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

Sponsors & Collaborators

• Freeman-Sheldon Research Group, Inc.: lead

Study Sites (1)

Freeman-Sheldon Research Group, Inc. Headquarters

Buckhannon, West Virginia, 26201, United States

Location

Related Publications (9)

• 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.

  PMID: 3723551 BACKGROUND

• 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.

  PMID: 16642020 BACKGROUND

• 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.

  PMID: 16510655 BACKGROUND

• 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.

  BACKGROUND

• 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.

  PMID: 15956637 BACKGROUND

• McCormick RJ. A Proposal for a Thesis: Heat Tolerance in Exercising Lean and Obese Middle-Aged Men. DEd diss., the Pennsylvania State University, 1973.

  BACKGROUND

• 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.

  PMID: 19436827 BACKGROUND

• 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.

  PMID: 2245110 BACKGROUND

• 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.

  PMID: 19050005 BACKGROUND

Biospecimen

Retention: NONE RETAINED

Blood samples will be taken but no retention is expected.

MeSH Terms

Conditions

Arthrogryposis; Craniofacial Abnormalities

Interventions

Lactic Acid; Glucose; Hematologic Tests; Adenosine Triphosphate; Glucose Tolerance Test; Blood Glucose; Exercise Test; Health Records, Personal; Restraint, Physical; Independent Medical Evaluation; Gait Analysis; Interview, Psychological

Condition Hierarchy (Ancestors)

Joint Diseases; Musculoskeletal Diseases; Muscular Diseases; Musculoskeletal Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Lactates; Hydroxy Acids; Carboxylic Acids; Organic Chemicals; Hexoses; Monosaccharides; Sugars; Carbohydrates; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides; Blood Chemical Analysis; Clinical Chemistry Tests; Diagnostic Techniques, Endocrine; Heart Function Tests; Diagnostic Techniques, Cardiovascular; Respiratory Function Tests; Diagnostic Techniques, Respiratory System; Ergometry; Medical Records; Records; Data Collection; Epidemiologic Methods; Behavior Control; Therapeutics; Immobilization; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Gait; Physical Examination; Physical Functional Performance; Physical Fitness; Health; Population Characteristics; Psychological Techniques; Behavioral Disciplines and Activities

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2011
• First Posted: March 2, 2011
• Study Start: March 1, 2014
• Primary Completion: June 1, 2022
• Study Completion: June 1, 2022
• Last Updated: June 6, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)