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出境医 / 临床实验 / Expiratory Muscle Strength Training (EMST) in Neuromuscular Disorders

Expiratory Muscle Strength Training (EMST) in Neuromuscular Disorders

Study Description
Brief Summary:
The purpose of this study is to investigate the impact of expiratory muscle strength training (EMST) on the swallowing, breathing, oral intake, quality of life and cough function of people with oculopharyngeal muscular dystrophy (OPMD).

Condition or disease Intervention/treatment Phase
Oculopharyngeal Muscular Dystrophy Muscular Dystrophies Myopathy; Hereditary Device: Expiratory muscle strength therapy (EMST150, Aspire LLC) Not Applicable

Detailed Description:

Outline:

Twenty participants with OPMD, with dysphagia, will be recruited from Neuromuscular clinics within Calgary. The investigators will enrol patients in a parallel group, sham-controlled, randomized clinical trial, with 10 participants in each group (active EMST and sham EMST).

Participants will have baseline measurements of: (i) global swallowing function via modified barium swallow study, (ii) maximum expiratory pressure, (iii) voluntary cough spirometry, (iv) forced vital capacity, (v) functional oral intake, (vi) patient report of self-perceived swallowing impairment (EAT-10 Questionnaire), and (vii) biomarker analyses.

Participants will undergo 5-weeks of EMST (active or sham). All baseline measurements will be repeated after 5-weeks of EMST and 10-weeks post-EMST to measure durability of effect.

Outcomes:

The end-goal of the current research is to obtain preliminary data for the benefit of EMST in a new study population, and direct future studies that may provide evidence for a new standard of care in treating neuromuscular diagnoses.

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Parallel group, double blind, sham controlled study
Masking: Double (Participant, Outcomes Assessor)
Masking Description: Participants will not be informed until the end of study whether they received active intervention or sham intervention
Primary Purpose: Treatment
Official Title: Interventional Study of Expiratory Muscle Strength Training as a Treatment in Neuromuscular Disorders
Estimated Study Start Date : July 1, 2021
Estimated Primary Completion Date : July 1, 2022
Estimated Study Completion Date : July 1, 2022
Arms and Interventions
Arm Intervention/treatment
Experimental: EMST therapy
Participants use the EMST device as per study protocol, set to 50% of the patient's maximal expiratory pressure, as measured by handheld manometer.
 Device: Expiratory muscle strength therapy (EMST150, Aspire LLC)
Active therapy calibrated to the participant's maximum expiratory pressure
Sham Comparator: Sham EMST therapy
Participants use a sham EMST device that has the spring removed as per study protocol, with no significant airflow resistance.
 Device: Expiratory muscle strength therapy (EMST150, Aspire LLC)
Active therapy calibrated to the participant's maximum expiratory pressure
Outcome Measures
Primary Outcome Measures :
  1. Global Swallowing Function [ Time Frame: Change in score from week 0 to week 5 ]
    Global swallowing function is rated from videofluoroscopy swallowing studies (VFSS), using the Dynamic Imaging Grade of Swallowing Toxicity (DIGEST), a validated 5-point scale. Global swallowing function is rated from 0-4: 0 = no pharyngeal dysphagia; 1 = mild; 2 = moderate; 3 = severe; 4 = life-threatening. A lower score is a better outcome.


Secondary Outcome Measures :
  1. Global Swallowing Function [ Time Frame: Change in score from week 0 to week 15; change in score from week 5 to week 15. ]
    Global swallowing function is rated from videofluoroscopy swallowing studies (VFSS), using the Dynamic Imaging Grade of Swallowing Toxicity (DIGEST), a validated 5-point scale. Global swallowing function is rated from 0-4: 0 = no pharyngeal dysphagia; 1 = mild; 2 = moderate; 3 = severe; 4 = life-threatening.

  2. Maximum expiratory pressure (MEP) [ Time Frame: Change in score from week 0 to week 5; change in score from week 0 to week 15; change in score from week 5 to week 15. ]
    MEP is a measure of respiratory muscle strength and is assessed with a handheld manometer, measured in centimetres of water (cmH2O). A higher score is a better outcome.

  3. Volitional cough strength (peak cough flow) [ Time Frame: Change in score from week 0 to week 5; change in score from week 0 to week 15; change in score from week 5 to week 15. ]
    Measure of cough strength that is assessed using a spirometer, measured in litres per minute (L/min). A higher score is a better outcome.

  4. Forced vital capacity (FVC) [ Time Frame: Change in score from week 0 to week 5; change in score from week 0 to week 15; change in score from week 5 to week 15. ]
    Measure of how much air is exhaled during forced exhalation and is assessed with a spirometer, measured in litres. A higher score is a better outcome.

  5. Oral Intake [ Time Frame: Change in score from week 0 to week 5; change in score from week 0 to week 15; change in score from week 5 to week 15. ]
    A measure daily nutritional and hydration consumption. Oral intake is assessed using the Functional Oral Intake Scale (FOIS), a validated 7-point ordinal scale (1 = no oral intake; 2 = tube dependent with minimal/inconsistent oral intake; 3 = tube supplements with consistent oral intake; 4 = total oral intake in single consistency; 5 = total oral intake of multiple consistencies requiring special preparation; 6 = total oral intake with no special preparation, but must avoid specific foods or liquid items; 7 = total oral intake with no restrictions). A higher score is a better outcome.

  6. Self-perceived swallowing impairment [ Time Frame: Change in score from week 0 to week 5; change in score from week 0 to week 15; change in score from week 5 to week 15. ]
    Will be measured using the Eating Assessment Tool-10 (EAT-10), a self-administered, symptom-specific outcome instrument for dysphagia. The EAT-10 allows patients to rate their swallowing symptoms on scale of 0 = no problem to 4 = severe problem. A lower score is a better outcome.

  7. Biomarker analyses [ Time Frame: Baseline measurement (week 0) ]
    An optional blood sample will be collected for biomarker analysis, to identify correlations with clinical response. We will measure genetic biomarkers associated with swallowing function including rs6265, rs165599, rs10835211, rs17601696, and APOE4 genotype status. For these 5 genetic biomarkers, participants will be scored as having zero, one, or two alleles. This information will be used in subgroup analyses for the primary and secondary outcomes.


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of oculopharyngeal muscular dystrophy (OPMD)
  • 18 years of age or older
  • Must be capable of providing informed consent
  • Must be able to undergo respiratory function testing and swallowing studies
  • Must have a forced vital capacity (FVC) greater than 60%
  • A score of 3 or greater on the Eating Assessment Tool-10 (EAT-10; self-administered, symptom-specific outcome instrument for dysphagia. A score of 3 or greater indicates increased stress around eating)
  • A score of 26 or greater on the Montreal Cognitive Assessment (MoCA; 30-point screening assessment used for detecting cognitive impairment. A score of 26 or greater is considered to be within functional limits.)

Exclusion Criteria:

  • Severe coronary artery disease
  • Acute myocardial infarction
  • Moderate to severe hypovolemia
  • Acute neurological events
  • Unstable cardiac status
  • Recent hernia
  • Severe chronic obstructive pulmonary disease (COPD)
  • Uncontrolled reflux issues
  • Women who are pregnant, or who suspect they may be pregnant
  • Cognitive impairment that would prevent comprehension of instructions and adherence to intervention guidelines (a score of less than 26 points on the MoCA)
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Robyn Wells, MSc 403-483-2277 robyn.wells@ucalgary.ca
Contact: Gerald Pfeffer, MD, PhD 403-210-3926 gerald.pfeffer@ucalgary.ca

Sponsors and Collaborators
University of Calgary
Muscular Dystrophy Canada
Investigators
Layout table for investigator information
Principal Investigator: Gerald Pfeffer, MD, PhD University of Calgary
Tracking Information
First Submitted Date  ICMJE June 6, 2019
First Posted Date  ICMJE July 5, 2019
Last Update Posted Date March 24, 2020
Estimated Study Start Date  ICMJE July 1, 2021
Estimated Primary Completion Date July 1, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 2, 2019) 		Global Swallowing Function [ Time Frame: Change in score from week 0 to week 5 ]
Global swallowing function is rated from videofluoroscopy swallowing studies (VFSS), using the Dynamic Imaging Grade of Swallowing Toxicity (DIGEST), a validated 5-point scale. Global swallowing function is rated from 0-4: 0 = no pharyngeal dysphagia; 1 = mild; 2 = moderate; 3 = severe; 4 = life-threatening. A lower score is a better outcome.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 2, 2019)
  • Global Swallowing Function [ Time Frame: Change in score from week 0 to week 15; change in score from week 5 to week 15. ]
    Global swallowing function is rated from videofluoroscopy swallowing studies (VFSS), using the Dynamic Imaging Grade of Swallowing Toxicity (DIGEST), a validated 5-point scale. Global swallowing function is rated from 0-4: 0 = no pharyngeal dysphagia; 1 = mild; 2 = moderate; 3 = severe; 4 = life-threatening.
  • Maximum expiratory pressure (MEP) [ Time Frame: Change in score from week 0 to week 5; change in score from week 0 to week 15; change in score from week 5 to week 15. ]
    MEP is a measure of respiratory muscle strength and is assessed with a handheld manometer, measured in centimetres of water (cmH2O). A higher score is a better outcome.
  • Volitional cough strength (peak cough flow) [ Time Frame: Change in score from week 0 to week 5; change in score from week 0 to week 15; change in score from week 5 to week 15. ]
    Measure of cough strength that is assessed using a spirometer, measured in litres per minute (L/min). A higher score is a better outcome.
  • Forced vital capacity (FVC) [ Time Frame: Change in score from week 0 to week 5; change in score from week 0 to week 15; change in score from week 5 to week 15. ]
    Measure of how much air is exhaled during forced exhalation and is assessed with a spirometer, measured in litres. A higher score is a better outcome.
  • Oral Intake [ Time Frame: Change in score from week 0 to week 5; change in score from week 0 to week 15; change in score from week 5 to week 15. ]
    A measure daily nutritional and hydration consumption. Oral intake is assessed using the Functional Oral Intake Scale (FOIS), a validated 7-point ordinal scale (1 = no oral intake; 2 = tube dependent with minimal/inconsistent oral intake; 3 = tube supplements with consistent oral intake; 4 = total oral intake in single consistency; 5 = total oral intake of multiple consistencies requiring special preparation; 6 = total oral intake with no special preparation, but must avoid specific foods or liquid items; 7 = total oral intake with no restrictions). A higher score is a better outcome.
  • Self-perceived swallowing impairment [ Time Frame: Change in score from week 0 to week 5; change in score from week 0 to week 15; change in score from week 5 to week 15. ]
    Will be measured using the Eating Assessment Tool-10 (EAT-10), a self-administered, symptom-specific outcome instrument for dysphagia. The EAT-10 allows patients to rate their swallowing symptoms on scale of 0 = no problem to 4 = severe problem. A lower score is a better outcome.
  • Biomarker analyses [ Time Frame: Baseline measurement (week 0) ]
    An optional blood sample will be collected for biomarker analysis, to identify correlations with clinical response. We will measure genetic biomarkers associated with swallowing function including rs6265, rs165599, rs10835211, rs17601696, and APOE4 genotype status. For these 5 genetic biomarkers, participants will be scored as having zero, one, or two alleles. This information will be used in subgroup analyses for the primary and secondary outcomes.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Expiratory Muscle Strength Training (EMST) in Neuromuscular Disorders
Official Title  ICMJE Interventional Study of Expiratory Muscle Strength Training as a Treatment in Neuromuscular Disorders
Brief Summary The purpose of this study is to investigate the impact of expiratory muscle strength training (EMST) on the swallowing, breathing, oral intake, quality of life and cough function of people with oculopharyngeal muscular dystrophy (OPMD).
Detailed Description

Outline:

Twenty participants with OPMD, with dysphagia, will be recruited from Neuromuscular clinics within Calgary. The investigators will enrol patients in a parallel group, sham-controlled, randomized clinical trial, with 10 participants in each group (active EMST and sham EMST).

Participants will have baseline measurements of: (i) global swallowing function via modified barium swallow study, (ii) maximum expiratory pressure, (iii) voluntary cough spirometry, (iv) forced vital capacity, (v) functional oral intake, (vi) patient report of self-perceived swallowing impairment (EAT-10 Questionnaire), and (vii) biomarker analyses.

Participants will undergo 5-weeks of EMST (active or sham). All baseline measurements will be repeated after 5-weeks of EMST and 10-weeks post-EMST to measure durability of effect.

Outcomes:

The end-goal of the current research is to obtain preliminary data for the benefit of EMST in a new study population, and direct future studies that may provide evidence for a new standard of care in treating neuromuscular diagnoses.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Parallel group, double blind, sham controlled study
Masking: Double (Participant, Outcomes Assessor)
Masking Description:
Participants will not be informed until the end of study whether they received active intervention or sham intervention
Primary Purpose: Treatment
Condition  ICMJE
  • Oculopharyngeal Muscular Dystrophy
  • Muscular Dystrophies
  • Myopathy; Hereditary
Intervention  ICMJE Device: Expiratory muscle strength therapy (EMST150, Aspire LLC)
Active therapy calibrated to the participant's maximum expiratory pressure
Study Arms  ICMJE
  • Experimental: EMST therapy
    Participants use the EMST device as per study protocol, set to 50% of the patient's maximal expiratory pressure, as measured by handheld manometer.
    Intervention: Device: Expiratory muscle strength therapy (EMST150, Aspire LLC)
  • Sham Comparator: Sham EMST therapy
    Participants use a sham EMST device that has the spring removed as per study protocol, with no significant airflow resistance.
    Intervention: Device: Expiratory muscle strength therapy (EMST150, Aspire LLC)
Publications *
  • Ertekin C, Yüceyar N, Aydoğdu, Karasoy H. Electrophysiological evaluation of oropharyngeal swallowing in myotonic dystrophy. J Neurol Neurosurg Psychiatry. 2001 Mar;70(3):363-71.
  • Luchesi KF, Kitamua S, Mourão LF. Amyotrophic Lateral Sclerosis survival analysis: Swallowing and non-oral feeding. NeuroRehabilitation. 2014;35(3):535-42. doi: 10.3233/NRE-141149.
  • Chiò A, Logroscino G, Hardiman O, Swingler R, Mitchell D, Beghi E, Traynor BG; Eurals Consortium. Prognostic factors in ALS: A critical review. Amyotroph Lateral Scler. 2009 Oct-Dec;10(5-6):310-23. doi: 10.3109/17482960802566824. Review.
  • Paris G, Martinaud O, Petit A, Cuvelier A, Hannequin D, Roppeneck P, Verin E. Oropharyngeal dysphagia in amyotrophic lateral sclerosis alters quality of life. J Oral Rehabil. 2013 Mar;40(3):199-204. doi: 10.1111/joor.12019. Epub 2012 Dec 27.
  • Yang R, Huang R, Chen D, Song W, Zeng Y, Zhao B, Zhou D, Shang HF. Causes and places of death of patients with amyotrophic lateral sclerosis in south-west China. Amyotroph Lateral Scler. 2011 May;12(3):206-9. doi: 10.3109/17482968.2011.572979. Epub 2011 Apr 21.
  • Abu-Baker A, Rouleau GA. Oculopharyngeal muscular dystrophy: recent advances in the understanding of the molecular pathogenic mechanisms and treatment strategies. Biochim Biophys Acta. 2007 Feb;1772(2):173-85. Epub 2006 Oct 11. Review.
  • Duranceau CA, Letendre J, Clermont RJ, Lévesque HP, Barbeau A. Oropharyngeal dysphagia in patients with oculopharyngeal muscular dystrophy. Can J Surg. 1978 Jul;21(4):326-9.
  • Pitts T, Bolser D, Rosenbek J, Troche M, Okun MS, Sapienza C. Impact of expiratory muscle strength training on voluntary cough and swallow function in Parkinson disease. Chest. 2009 May;135(5):1301-1308. doi: 10.1378/chest.08-1389. Epub 2008 Nov 24.
  • Troche MS, Okun MS, Rosenbek JC, Musson N, Fernandez HH, Rodriguez R, Romrell J, Pitts T, Wheeler-Hegland KM, Sapienza CM. Aspiration and swallowing in Parkinson disease and rehabilitation with EMST: a randomized trial. Neurology. 2010 Nov 23;75(21):1912-9. doi: 10.1212/WNL.0b013e3181fef115.
  • Silverman EP, Miller S, Zhang Y, Hoffman-Ruddy B, Yeager J, Daly JJ. Effects of expiratory muscle strength training on maximal respiratory pressure and swallow-related quality of life in individuals with multiple sclerosis. Mult Scler J Exp Transl Clin. 2017 May 29;3(2):2055217317710829. doi: 10.1177/2055217317710829. eCollection 2017 Apr-Jun.
  • Jones HN, Crisp KD, Robey RR, Case LE, Kravitz RM, Kishnani PS. Respiratory muscle training (RMT) in late-onset Pompe disease (LOPD): Effects of training and detraining. Mol Genet Metab. 2016 Feb;117(2):120-8. doi: 10.1016/j.ymgme.2015.09.003. Epub 2015 Sep 8.
  • Plowman EK, Tabor-Gray L, Rosado KM, Vasilopoulos T, Robison R, Chapin JL, Gaziano J, Vu T, Gooch C. Impact of expiratory strength training in amyotrophic lateral sclerosis: Results of a randomized, sham-controlled trial. Muscle Nerve. 2019 Jan;59(1):40-46. doi: 10.1002/mus.26292. Epub 2018 Nov 29.
  • Plowman EK, Watts SA, Tabor L, Robison R, Gaziano J, Domer AS, Richter J, Vu T, Gooch C. Impact of expiratory strength training in amyotrophic lateral sclerosis. Muscle Nerve. 2016 Jun;54(1):48-53. doi: 10.1002/mus.24990. Epub 2016 Mar 3.
  • Rosenbek JC, Robbins JA, Roecker EB, Coyle JL, Wood JL. A penetration-aspiration scale. Dysphagia. 1996 Spring;11(2):93-8.
  • Nimmons D, Pendleton N, Payton A, Ollier W, Horan M, Wilkinson J, Hamdy S. A novel association between COMT and BDNF gene polymorphisms and likelihood of symptomatic dysphagia in older people. Neurogastroenterol Motil. 2015 Sep;27(9):1223-31. doi: 10.1111/nmo.12609. Epub 2015 Jun 14.
  • Raginis-Zborowska A, Pendleton N, Hamdy S. Genetic determinants of swallowing impairment, recovery and responsiveness to treatment. Curr Phys Med Rehabil Rep. 2016;4(4):249-256. doi: 10.1007/s40141-016-0133-6. Epub 2016 Aug 8. Review.
  • Robison R, Tabor-Gray LC, Wymer JP, Plowman EK. Combined respiratory training in an individual with C9orf72 amyotrophic lateral sclerosis. Ann Clin Transl Neurol. 2018 Aug 21;5(9):1134-1138. doi: 10.1002/acn3.623. eCollection 2018 Sep.
  • Tabor LC, Rosado KM, Robison R, Hegland K, Humbert IA, Plowman EK. Respiratory training in an individual with amyotrophic lateral sclerosis. Ann Clin Transl Neurol. 2016 Sep 1;3(10):819-823. eCollection 2016 Oct.
  • Belafsky PC, Mouadeb DA, Rees CJ, Pryor JC, Postma GN, Allen J, Leonard RJ. Validity and reliability of the Eating Assessment Tool (EAT-10). Ann Otol Rhinol Laryngol. 2008 Dec;117(12):919-24.
  • Crary MA, Mann GD, Groher ME. Initial psychometric assessment of a functional oral intake scale for dysphagia in stroke patients. Arch Phys Med Rehabil. 2005 Aug;86(8):1516-20.
  • Hutcheson KA, Barrow MP, Barringer DA, Knott JK, Lin HY, Weber RS, Fuller CD, Lai SY, Alvarez CP, Raut J, Lazarus CL, May A, Patterson J, Roe JW, Starmer HM, Lewin JS. Dynamic Imaging Grade of Swallowing Toxicity (DIGEST): Scale development and validation. Cancer. 2017 Jan 1;123(1):62-70. doi: 10.1002/cncr.30283. Epub 2016 Aug 26.
  • Plowman EK, Tabor LC, Robison R, Gaziano J, Dion C, Watts SA, Vu T, Gooch C. Discriminant ability of the Eating Assessment Tool-10 to detect aspiration in individuals with amyotrophic lateral sclerosis. Neurogastroenterol Motil. 2016 Jan;28(1):85-90. doi: 10.1111/nmo.12700. Epub 2015 Oct 28.
  • Chiara T, Martin AD, Davenport PW, Bolser DC. Expiratory muscle strength training in persons with multiple sclerosis having mild to moderate disability: effect on maximal expiratory pressure, pulmonary function, and maximal voluntary cough. Arch Phys Med Rehabil. 2006 Apr;87(4):468-73.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: July 2, 2019) 		20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 1, 2022
Estimated Primary Completion Date July 1, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosis of oculopharyngeal muscular dystrophy (OPMD)
  • 18 years of age or older
  • Must be capable of providing informed consent
  • Must be able to undergo respiratory function testing and swallowing studies
  • Must have a forced vital capacity (FVC) greater than 60%
  • A score of 3 or greater on the Eating Assessment Tool-10 (EAT-10; self-administered, symptom-specific outcome instrument for dysphagia. A score of 3 or greater indicates increased stress around eating)
  • A score of 26 or greater on the Montreal Cognitive Assessment (MoCA; 30-point screening assessment used for detecting cognitive impairment. A score of 26 or greater is considered to be within functional limits.)

Exclusion Criteria:

  • Severe coronary artery disease
  • Acute myocardial infarction
  • Moderate to severe hypovolemia
  • Acute neurological events
  • Unstable cardiac status
  • Recent hernia
  • Severe chronic obstructive pulmonary disease (COPD)
  • Uncontrolled reflux issues
  • Women who are pregnant, or who suspect they may be pregnant
  • Cognitive impairment that would prevent comprehension of instructions and adherence to intervention guidelines (a score of less than 26 points on the MoCA)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Robyn Wells, MSc 403-483-2277 robyn.wells@ucalgary.ca
Contact: Gerald Pfeffer, MD, PhD 403-210-3926 gerald.pfeffer@ucalgary.ca
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04009408
Other Study ID Numbers  ICMJE REB18-1121
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of Calgary
Study Sponsor  ICMJE University of Calgary
Collaborators  ICMJE Muscular Dystrophy Canada
Investigators  ICMJE
Principal Investigator: Gerald Pfeffer, MD, PhD University of Calgary
PRS Account University of Calgary
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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