Phelan-McDermid SyndromeNCT02000167
Mitochondrial Dysfunction in Phelan-McDermid Syndrome
An observational study of Phelan-McDermid Syndrome, run by University of Arkansas at 1 site in United States.
Trial summary
The purpose of this study is to determine whether a relationship exists between gene deletion(s) specific to the mitochondrial electron transport chain and presentation of clinical characteristics in patients with Phelan-McDermid Syndrome (PMS). Read more about this study
- Who is it for?
- Ages 1 year to 21 years
- Conditions the study is for
- Phelan-McDermid Syndrome
- How many people
- 51 participants
- Where
- 1 siteUnited States
- Study dates
- May 2012to May 2015
- Phase
- Observational
- Are there results?
- None posted in the registry
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 year to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Patients will be identified through the registry for this specific aim. PMS patients in the registry will be offered to be entered the study.
Who may be able to join
- 1-21 years of age
- Diagnosed with Phelan-McDermid Syndrome AND diagnosed with Mitochondrial Disorder
- Diagnosed with Phelan-McDermid Syndrome
Who cannot join
- none
Trial locations and contacts
1 site in 1 country.
United States1 site
Arkansas Children's Hospital Research Institute
Little Rock, Arkansas, 72205
About this study
Official title: Mitochondrial Dysfunction in Phelan-McDermid Syndrome: Explaining Clinical Variation and Providing a Path Towards Treatment
The purpose of this study is to determine whether a relationship exists between gene deletion(s) specific to the mitochondrial electron transport chain and presentation of clinical characteristics in patients with Phelan-McDermid Syndrome (PMS).
Read the detailed description
Phelan-McDermid Syndrome (PMS) results from a deletion within the 22q13 chromosome region. Most children have specific physical morphology and developmental delays with many displaying characteristics of autism spectrum disorder (ASD) including abnormalities in social development. The behavioral aspect of PMS that parallels ASD has raised particular interest as the SHANK3 gene, which lies in the 22q13 region, is important for synaptic development, and animal SHANK3 knockout models demonstrate ASD characteristics thereby confirming the importance of this gene in PMS. However, despite the importance of the SHANK3 gene, individuals with PMS have variations in their development, behavior and medical characteristics that cannot be fully explained by the SHANK3 deletion.
Recently, Frye (2012) has noted the existence of 6 mitochondrial genes that lie slightly proximal to the SHANK3 gene within the 22q13 region. These include genes important electron transport change function (SCO2, NDUFA6), mitochondrial DNA (TYMP) and RNA (TRMU) metabolism, fatty acid metabolism (CPT1B) and tricarboxylic acid cycle function (ACO2). Since most Individuals with PMS have deletions that include chromosomal deletion outside of the SHANK3 region, it is very likely that many, if not most, of children with PMS may have deletions in these mitochondrial genes. Many of these genes have been linked to mitochondrial disease, even in the heterozygous state. Even if recognized, mitochondrial disease is only linked to a homozygous abnormal state (autosomal recessive), the loss of one gene (heterozygous state) could result in symptomatology when associated with deletions in other mitochondrial or non-mitochondrial genes. Abnormalities in mitochondrial pathways can result in neurologic and non-neurologic symptoms including those sometimes seen in children with PMS. Added with the SHANK3 deletion, abnormalities in these mitochondrial genes could explain variations in patterns of development and the eventual cognitive potential.
References: Frye RE. Mitochondrial disease in 22q13 duplication syndrome. J Child Neurol. 2012; 27(7):942-9.
- Conditions
- Phelan-McDermid Syndrome
- Keywords
- Electron Transport Chain, Mitochondrial Disease, Chromosomal Deletion
- Medical subject headings
- Telomeric 22q13 Monosomy Syndrome, Mitochondrial Diseases, Chromosome Deletion
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 |
|---|---|---|
| Phelan-McDermid Syndrome only | Diagnosed with Phelan-McDermid Syndrome; 50 subjects to be recruited. 1-21 years of age | |
| Co-morbid Phelan-McDermid Syndrome & Mitochodrial Disorder | 1-21 years of age; Diagnosed with Phelan-McDermid Syndrome AND diagnosed with Mitochondrial Disorder; 50 subjects to be recruited. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Electron Transport Chain function derived from buccal cells of known PMS patients
Electron transport chain (ETC) function will be measured in cells collected using Buccal swabs to determine if certain PMS patients symptomatology and clinical characteristics/variations can be explained due to variations in patterns of ETC function in this cohort
Measured: Up to two years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2013 (estimated)
- Study startMay 2012
- Primary completionMay 2015
- Study completionMay 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Phelan-McDermid SyndromeStudies 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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Arkansas
- Sponsor type
- University, hospital or other
- Collaborators
- St. Christopher's Hospital for Children
- Responsible party
- Sponsor
- Investigators
- Richard E Frye, M.D./Ph.D., Principal investigator, University of Arkansas for Medical Sciences; Arkansas Children's Hospital Research InstituteMichael J Goldenthal, Ph.D., Principal investigator, Drexel University College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02000167
- Sponsor's protocol ID
- 136271
- Status last verified
- Jun 2015
- First submitted
- 25 Nov 2013
- Last updated
- 5 Aug 2021
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mitochondrial Dysfunction in Phelan-McDermid Syndrome: Explaining Clinical Variation and Providing a Path Towards Treatment
- ClinicalTrials.gov ID
- NCT02000167
- Acronym / sponsor ID
- 136271
- Conditions
- Phelan-McDermid Syndrome
- Keywords
- Electron Transport Chain, Mitochondrial Disease, Chromosomal Deletion
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- University of ArkansasUniversity, hospital or other
- Collaborators
- St. Christopher's Hospital for Children
- Study start
- May 2012
- Primary completion
- May 2015 (actual)
- Study completion
- May 2015 (actual)
- First posted
- 3 Dec 2013 (estimated)
- 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.
The purpose of this study is to determine whether a relationship exists between gene deletion(s) specific to the mitochondrial electron transport chain and presentation of clinical characteristics in patients with Phelan-McDermid Syndrome (PMS).
Detailed description
Phelan-McDermid Syndrome (PMS) results from a deletion within the 22q13 chromosome region. Most children have specific physical morphology and developmental delays with many displaying characteristics of autism spectrum disorder (ASD) including abnormalities in social development. The behavioral aspect of PMS that parallels ASD has raised particular interest as the SHANK3 gene, which lies in the 22q13 region, is important for synaptic development, and animal SHANK3 knockout models demonstrate ASD characteristics thereby confirming the importance of this gene in PMS. However, despite the importance of the SHANK3 gene, individuals with PMS have variations in their development, behavior and medical characteristics that cannot be fully explained by the SHANK3 deletion.
Recently, Frye (2012) has noted the existence of 6 mitochondrial genes that lie slightly proximal to the SHANK3 gene within the 22q13 region. These include genes important electron transport change function (SCO2, NDUFA6), mitochondrial DNA (TYMP) and RNA (TRMU) metabolism, fatty acid metabolism (CPT1B) and tricarboxylic acid cycle function (ACO2). Since most Individuals with PMS have deletions that include chromosomal deletion outside of the SHANK3 region, it is very likely that many, if not most, of children with PMS may have deletions in these mitochondrial genes. Many of these genes have been linked to mitochondrial disease, even in the heterozygous state. Even if recognized, mitochondrial disease is only linked to a homozygous abnormal state (autosomal recessive), the loss of one gene (heterozygous state) could result in symptomatology when associated with deletions in other mitochondrial or non-mitochondrial genes. Abnormalities in mitochondrial pathways can result in neurologic and non-neurologic symptoms including those sometimes seen in children with PMS. Added with the SHANK3 deletion, abnormalities in these mitochondrial genes could explain variations in patterns of development and the eventual cognitive potential.
References: Frye RE. Mitochondrial disease in 22q13 duplication syndrome. J Child Neurol. 2012; 27(7):942-9.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phelan-McDermid Syndrome only | – | –Diagnosed with Phelan-McDermid Syndrome; 50 subjects to be recruited. 1-21 years of age |
| Co-morbid Phelan-McDermid Syndrome & Mitochodrial Disorder | – | –1-21 years of age; Diagnosed with Phelan-McDermid Syndrome AND diagnosed with Mitochondrial Disorder; 50 subjects to be recruited. |
Who may qualify
- Ages
- 1 year to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Patients will be identified through the registry for this specific aim. PMS patients in the registry will be offered to be entered the study.
Key inclusion criteria (3 listed)
- 1-21 years of age
- Diagnosed with Phelan-McDermid Syndrome AND diagnosed with Mitochondrial Disorder
- Diagnosed with Phelan-McDermid Syndrome
Key exclusion criteria (1 listed)
- none
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
Electron Transport Chain function derived from buccal cells of known PMS patients
Time frame: Up to two years
Electron transport chain (ETC) function will be measured in cells collected using Buccal swabs to determine if certain PMS patients symptomatology and clinical characteristics/variations can be explained due to variations in patterns of ETC function in this cohort
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Aug 2021.
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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. This study is not recruiting at the moment.
Richard E Frye, M.D./Ph.D. principal investigator
University of Arkansas for Medical Sciences; Arkansas Children's Hospital Research Institute
Michael J Goldenthal, Ph.D. principal investigator
Drexel University College of Medicine
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 Phelan-McDermid Syndrome, run by University of Arkansas 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 3 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: finished, as of the sponsor's last update on 5 Aug 2021. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Electron Transport Chain function derived from buccal cells of known PMS patients (time frame: Up to two years). 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 5 Aug 2021; AzTrials last refreshed its copy on 27 Oct 2026.