The classic website will no longer be available as of June 25, 2024. Please use the modernized ClinicalTrials.gov.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

MEHMO Natural History and Biomarkers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT06019182
Recruitment Status : Recruiting
First Posted : August 31, 2023
Last Update Posted : May 20, 2024
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) )

Study Description
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:

This observational natural history study will follow individuals with MEHMO (Mental disability, Epileptic seizure, Hypopituitarism/Hypogenitalism, Microcephaly, Obesity) syndrome or an eIF2-pathway related disorder, who have symptoms such as intellectual delay, seizures, abnormal hormone and blood sugar levels, and decreased motor skills.

No current treatment for these conditions is available. A major impediment to the testing of potential therapeutic interventions is the lack of well-defined outcome measures. This protocol seeks to identify biochemical and clinical markers to monitor disease progression, and better understand the natural history of these conditions.

Any person diagnosed with MEHMO syndrome or related conditions, who can travel to the NIH Clinical Center can participate in this study.

The study involves:

  • General health assessment and evaluation
  • Imaging studies
  • Laboratory tests
  • Collection of blood, urine, spinal fluid, skin biopsy.

Condition or disease
Intellectual Disability Epilepsy Hypogonadisms Microcephaly Nervous System Malformations Obesity

Detailed Description:

Study Description: This is a prospective natural history study of individuals who have MEHMO syndrome or eIF2-pathway related conditions, or who are carriers of EIF2S3-related conditions to generate hypotheses for further understanding of disease pathophysiology, diagnosis, prognosis, management, and treatment. The protocol aims to enroll and follow affected or carrier individuals longitudinally to establish a repository of concurrent evaluations and biomaterials, as well as to enroll unaffected individuals for collection of informative comparable data and samples.

Objectives:

Primary Objective:

Characterize the presentation of MEHMO syndrome and eIF2 pathway related conditions.

Secondary Objectives:

  1. Identify disease-reflective fluid biomarkers
  2. Develop a disease severity rating scale or classification algorithm
  3. Assess tolerability and feasibility of study evaluations
  4. Establish a repository of participant data and samples for future research

Endpoints:

Primary Endpoint:

Frequency and time-to-event of signs and symptoms.

Secondary Endpoints:

  1. Mean difference of candidate fluid biomarkers level in affected versus carrier versus unaffected individuals
  2. Correlation of rating scale or classification algorithm to age, genotype, or other variables
  3. Frequency of completed evaluations and reasons for Noncompletion

Study Population: 25 affected individuals 1-week of age or older 25 EIF2S3-variant carrier individuals 1-month of age or older 50 unaffected individuals 1 month of age or older of any sex, race, ethnicity, geographic location who can participate without increased risk to personal health.

Study Design
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Observational
Estimated Enrollment : 150 participants
Observational Model: Cohort
Time Perspective: Other
Official Title: Investigations of Individuals With MEHMO Syndrome or eIF2-Pathway Related Conditions
Estimated Study Start Date : May 23, 2024
Estimated Primary Completion Date : September 1, 2053
Estimated Study Completion Date : September 1, 2053

Resource links provided by the National Library of Medicine


Groups and Cohorts
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Group/Cohort
Affected
Individuals who have MEHMO syndrome or eIF2-pathway related conditions 1-week of age or older.
Carrier
EIF2S3-variant carrier individuals 1-month of age or older.
Unaffected Non-carrier
Unaffected individuals 1 month of age or older who are 1st degree relative of an affected individual


Outcome Measures
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Characterize the presentation of MEHMO syndrome and eIF2-pathway related conditions. [ Time Frame: Ongoing ]
    Frequency and time-to-event of signs and symptoms. These will allow systematic and potentially quantitative measures of disease presentation that can then be operationalized to develop disease rating scale(s) and correlative measures for candidate biomarkers.


Secondary Outcome Measures :
  1. Identify disease-reflective fluid biomarkers [ Time Frame: Ongoing ]
    Difference and range of candidate fluid biomarkers level in affected vs. carrier vs. unaffected individuals. Sensitive or specific quantitative markers will allow for improved diagnosis, management, and treatment of MEHMO syndrome or eIF2-pathway related disorders.

  2. Develop a disease severity rating scale or classification algorithm. [ Time Frame: Ongoing ]
    A quantitative rating scale or classification algorithm that reflects other disease aspects will provide a standardized tool for communication amongst all involved in the clinical care and research of MEHMO syndrome or eIF2-pathway related disorders.

  3. Assess tolerability and feasibility of study evaluations. [ Time Frame: Ongoing ]
    Frequency of completed evaluations and reasons for non-completion will inform design of future trials for MEHMO syndrome or eIF2-pathway related disorders.

  4. Characterize EIF2S3-carrier phenotype. [ Time Frame: Ongoing ]
    Frequency and time-to-event of signs and symptoms at disease-relevant intervals will provide a systematic evaluation of EIF2S3- carrier phenotype.

  5. Establish a repository of participant data and samples for future research. [ Time Frame: Ongoing ]
    A repository of concurrently collected participant data and samples for future research will provide resources for future research towards understanding the disease and developing interventions.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   1 Week to 100 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Inclusion Criteria: An individual must be > 1-week of age if affected, or > 1-month of age if unaffected. For Screening: Have a combination of signs/symptoms suggestive of MEHMO syndrome, AND no or inconclusive molecular testing. For Main Study: 1. Have a combination of signs/symptoms suggestive of MEHMO syndrome, AND disease-associated variant(s) or variant(s) of uncertain significance in one of the eIF2-pathway related genes OR 2. Be a first-degree relative of an individual with EIF2S3-related MEHMO syndrome, AND a carrier of the pathogenic or likely pathogenic variant. OR 3. Be a non-affected, non-carrier family member of an individual with MEHMO syndrome or an eIF2-pathway related condition. Exclusion Criteria: Any individual who, in the opinion of the Investigators, is unable to comply with the protocol or have medical conditions that would potentially increase the risk of participation.
Criteria
  • Inclusion Criteria

To be eligible to participate in this study, an individual must meet the following criteria:

Be greater than or equal to 1-week of age if affected, or greater than or equal to 1-month of age if unaffected.

19

For Screening:

Have a combination of signs/symptoms suggestive of MEHMO syndrome, AND no or inconclusive molecular testing.

For Main Study

  1. Have a combination of signs/symptoms suggestive of MEHMO syndrome, AND disease-associated variant(s) or variant(s) of uncertain significance in one of the eIF2-

    pathway related genes

    OR

  2. Be a first-degree relative of an individual with EIF2S3-related MEHMO syndrome, AND a carrier of the pathogenic or likely pathogenic variant.

    OR

  3. Be a non-affected, non-carrier family member of an individual with MEHMO syndrome or an eIF2-pathway related condition.

Exclusion Criteria

Any individual who, in the opinion of the Investigators, is unable to comply with the protocol

or have medical conditions that would potentially increase the risk of participation will be

excluded from participation in this study.

Contacts and Locations
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06019182


Contacts
Layout table for location contacts
Contact: An N Dang Do, M.D. (301) 496-8849 an.dangdo@nih.gov

Locations
Layout table for location information
United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: An Dang Do, M.D.    301-496-8849    an.dangdo@nih.gov   
Sponsors and Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
Layout table for investigator information
Principal Investigator: An N Dang Do, M.D. Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
More Information
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information
Additional Information:

Layout table for additonal information
Responsible Party: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier: NCT06019182    
Other Study ID Numbers: 10001681
001681-CH
First Posted: August 31, 2023    Key Record Dates
Last Update Posted: May 20, 2024
Last Verified: December 6, 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: .Requests for sharing of relevant IPD for clinical management purpose or directly from the individual participant will be considered on case basis and are not guaranteed to result in sharing of IPD.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) ):
MEHMO
X-linked MEHMO Syndrome
eIF2-Pathway Related Conditions
EIF2S3
Additional relevant MeSH terms:
Layout table for MeSH terms
Microcephaly
Intellectual Disability
Nervous System Malformations
Hypogonadism
Nervous System Diseases
Congenital Abnormalities
Gonadal Disorders
Endocrine System Diseases
Neurobehavioral Manifestations
 Neurologic Manifestations
Neurodevelopmental Disorders
Mental Disorders
Craniofacial Abnormalities
Musculoskeletal Abnormalities
Musculoskeletal Diseases
Malformations of Cortical Development, Group I
Malformations of Cortical Development