Intellectual DisabilityNCT06019182
MEHMO Natural History and Biomarkers
An observational study of Intellectual Disability and Epilepsy, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 1 week to 100 years
- Conditions the study is for
- Intellectual Disability, Epilepsy, Hypogonadisms
- How many people
- 150 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Oct 2023to 1 Sep 2053
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 week to 100 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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.
Who may be able to join
- To be eligible to participate in this study, an individual must meet the following criteria:
- 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.
Show all 16Show fewer
- OR
- Be a relative of an individual with MEHMO syndrome/eIF2-related condition and whose genetic may be informative for research.
- For Main Study:
- 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
- Be a relative of an individual with MEHMO syndrome/eIF2-related condition, AND a carrier of the pathogenic or likely pathogenic variant.
- OR
- Be a non-affected, non-carrier family member of an individual with MEHMO syndrome or an eIF2-pathway related condition.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
An Dang Do, M.D., 301-496-8849, an.dangdo@nih.gov
About this study
Official title: Investigations of Individuals With MEHMO Syndrome or eIF2-Pathway Related Conditions
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.
Read more
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.
Read the 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:
- Identify disease-reflective fluid biomarkers
- Develop a disease severity rating scale or classification algorithm
- Assess tolerability and feasibility of study evaluations
- 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:
- Mean difference of candidate fluid biomarkers level in affected versus carrier versus unaffected individuals
- Correlation of rating scale or classification algorithm to age, genotype, or other variables
- Frequency of completed evaluations and reasons for noncompletion
- Conditions
- Intellectual Disability, Epilepsy, Hypogonadisms, Microcephaly, Nervous System Malformations, Obesity
- Keywords
- MEHMO, X-linked MEHMO Syndrome, eIF2-Pathway Related Conditions, EIF2S3
- Medical subject headings
- Intellectual Disability, Epilepsy, Microcephaly, Nervous System Malformations, Obesity, MEHMO syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Characterize the presentation of MEHMO syndrome and eIF2-pathway related conditions.
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.
Measured: Ongoing
Secondary outcomes (5)
Identify disease-reflective fluid biomarkers
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.
Measured: Ongoing
Develop a disease severity rating scale or classification algorithm.
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.
Measured: Ongoing
Assess tolerability and feasibility of study evaluations.
Frequency of completed evaluations and reasons for non-completion will inform design of future trials for MEHMO syndrome or eIF2-pathway related disorders.
Measured: Ongoing
Characterize EIF2S3-carrier phenotype.
Frequency and time-to-event of signs and symptoms at disease-relevant intervals will provide a systematic evaluation of EIF2S3- carrier phenotype.
Measured: Ongoing
Establish a repository of participant data and samples for future research.
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.
Measured: Ongoing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2023
- Study start23 Oct 2023
- Primary completion1 Sep 2053 (estimated)
- Study completion1 Sep 2053 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Intellectual DisabilityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- An N Dang Do, M.D., Principal investigator, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06019182
- Sponsor's protocol ID
- 10001681
- Other IDs
- 001681-CH
- Status last verified
- 23 Jun 2026
- First submitted
- 30 Aug 2023
- Last updated
- 25 Jun 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: 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.
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigations of Individuals With MEHMO Syndrome or eIF2-Pathway Related Conditions
- ClinicalTrials.gov ID
- NCT06019182
- Acronym / sponsor ID
- 10001681
- Conditions
- Intellectual Disability, Epilepsy, Hypogonadisms, Microcephaly, Nervous System Malformations, Obesity
- Keywords
- MEHMO, X-linked MEHMO Syndrome, eIF2-Pathway Related Conditions, EIF2S3
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)US National Institutes of Health
- Study start
- 23 Oct 2023 (actual)
- Primary completion
- 1 Sep 2053 (estimated)
- Study completion
- 1 Sep 2053 (estimated)
- First posted
- 31 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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:
- Identify disease-reflective fluid biomarkers
- Develop a disease severity rating scale or classification algorithm
- Assess tolerability and feasibility of study evaluations
- 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:
- Mean difference of candidate fluid biomarkers level in affected versus carrier versus unaffected individuals
- Correlation of rating scale or classification algorithm to age, genotype, or other variables
- Frequency of completed evaluations and reasons for noncompletion
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 1 week to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- 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.
Key inclusion criteria (16 listed)
- To be eligible to participate in this study, an individual must meet the following criteria:
- Be >= 1-week of age if affected, or >=1-month of age if unaffected.
- Have a combination of signs/symptoms suggestive of MEHMO syndrome,
- AND
- no or inconclusive molecular testing.
Key exclusion criteria (1 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
5 secondary outcomes
Identify disease-reflective fluid biomarkers
Time frame: Ongoing
Develop a disease severity rating scale or classification algorithm.
Time frame: Ongoing
Assess tolerability and feasibility of study evaluations.
Time frame: Ongoing
Characterize EIF2S3-carrier phenotype.
Time frame: Ongoing
Establish a repository of participant data and samples for future research.
Time frame: Ongoing
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
An N Dang Do, M.D. principal investigator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Intellectual Disability and Epilepsy, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 25 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact An N Dang Do, M.D. ((301) 496-8849, an.dangdo@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Characterize the presentation of MEHMO syndrome and eIF2-pathway related conditions. (time frame: Ongoing). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2026.