AutismNCT00917683
Investigation of Neuroserpin as an Autism Candidate Gene
An observational study of Autism, run by State University of New York - Upstate Medical University at 1 site in United States.
Trial summary
Previously it has been shown that Familial Encephalopathy with neuroserpin inclusion bodies (FENIB) patients develop abnormalities that partially overlap with Autism Spectrum disorders (ASD), confounded with additional features that could be explained by inclusion body formation not expected in subjects with inclusion… Read more about this study
- Who is it for?
- Ages 1 year and olderHealthy volunteers can take part
- Conditions the study is for
- Autism
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2009to Apr 2012
- 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 and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Autistic patients and their first degree relatives
Who may be able to join
- Autistic patient, or first degree relative of autistic patient
Who cannot join
- Less than one year of age.
Trial locations and contacts
1 site in 1 country.
United States1 site
SUNY Upstate Medical University
Syracuse, New York, 13210
About this study
Previously it has been shown that Familial Encephalopathy with neuroserpin inclusion bodies (FENIB) patients develop abnormalities that partially overlap with Autism Spectrum disorders (ASD), confounded with additional features that could be explained by inclusion body formation not expected in subjects with inclusion body forming SERPINI1 mutations. There is no described human neuroserpin deficiency phenotype. The neuroserpin knockout mouse phenotype also suggests a possible overlap with autism. Neuroserpin could contribute directly at the synapse or through altered neuron migration during early development leading to the "underconnectivity" that underlies autism by potentially contributing to the excess of short connections and not enough long ones seen in autistic brains, possibly due to an imbalance in pruning of neurons and synapses early in life. It is thus proposed to sequence the neuroserpin gene in initially 20, and subsequently up to 100 idiopathic autistic patients selected as having the language impairment and perseveration endophenotypes.
Read the detailed description
It is proposed to perform a pilot study to ask whether genetic variation at SERPINI1 is contributing to idiopathic autism. To maximize the chance of finding such variants, the perseveration and language delay endophenotypes (simpler intermediate traits) will be used to select twenty autistic multiplex (and if necessary singleplex) families with idiopathic autistic patients who have been evaluated with the Autism Diagnostic Interview-revised (ADI-R) and their nuclear families ( siblings and their parents) will be identified by Dr. Liptak and Dr. Lebel with the assistance of Ms Klausner and recruited. Patients with syndromic autism due to known causes such as fragile X syndrome, Tuberous sclerosis, Down syndrome, and Neurofibromatosis type I will be excluded. The entire SERPINI1 coding region (nine exons), one kilobase of promoter region (Chen, 2007) and at least 200 bp of intron flanking each exon will be sequenced in an index case and the segregation of mutations identified investigated within the families. All mutations that appear to be good functional candidates will be compared in frequency amongst autistic and control populations in order to determine if a case can be made that SERPINI1 could be contributing to autism. In addition, known neuroserpin SNPs identified through the Hapmap project (www.hapmap.org) will be investigated and tested for evidence of transmission distortion/disequilibrium by linkage/association analysis. Depending on the results from this initial experiment it is proposed to subsequently sequence up to a further 80 local autism patients (maximum of 100 patients). Additional studies would be performed as follow up studies to similarly sequence the genes of other serpins expressed in the brain; Plasminogen activator 1, PA1, SERPINE1 located at the MLS linkage peak at 7q22.1 seen in IMGSAC study (Lamb, 2002) while Proteinase nexin 1, PN1 SERPINE2 at 2q36.1,close to previously identified linkage peaks (Autism Genome Project consortium, 2007) and potentially their putative serine protease targets (tPA at 8p11.21 and uPA at 10q22.2) and the upstream neuroserpin activators (ALK6, AMH and BMP2) (Lebeurrier, 2008). tPA expression is increased by events that require synaptic plasticity (Yepes, 2002) and enhances NMDA receptor signaling by cleavage of its NR1 subunit (Pawlack, 2002). All interesting leads will be pursued by obtaining additional samples from the Autism Genetic Resource Exchange (AGRE)( www.agre.org), a publically available recourse of phenotypic data and bio-materials which provides diagnostic information and DNA from 100's of multiplex ASD families.
- Conditions
- Autism
- Medical subject headings
- Autistic Disorder
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 |
|---|---|---|
| 1 | Autistic patients. | |
| 2 | Matched controls |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine SERPIN1 gene sequence variation in autistic subjects.
Measured: one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2009 (estimated)
- Study startJun 2009
- Primary completionApr 2012
- Study completionApr 2012
Why it stopped: Lack of enrollment.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AutismStudies 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
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- State University of New York - Upstate Medical University
- Sponsor type
- University, hospital or other
- Investigators
- Antony E Shrimpton, PhD, Principal investigator, State University of New York - Upstate Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00917683
- Sponsor's protocol ID
- IRB#5811
- Status last verified
- Apr 2016
- First submitted
- 8 Jun 2009
- Last updated
- 19 Apr 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigation of Neuroserpin as an Autism Candidate Gene
- ClinicalTrials.gov ID
- NCT00917683
- Acronym / sponsor ID
- IRB#5811
- Conditions
- Autism
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Lack of enrollment.
- Enrolment
- 5 participants (actual)
- Lead sponsor
- State University of New York - Upstate Medical UniversityUniversity, hospital or other
- Study start
- Jun 2009
- Primary completion
- Apr 2012 (actual)
- Study completion
- Apr 2012 (actual)
- First posted
- 10 Jun 2009 (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.
Previously it has been shown that Familial Encephalopathy with neuroserpin inclusion bodies (FENIB) patients develop abnormalities that partially overlap with Autism Spectrum disorders (ASD), confounded with additional features that could be explained by inclusion body formation not expected in subjects with inclusion body forming SERPINI1 mutations. There is no described human neuroserpin deficiency phenotype. The neuroserpin knockout mouse phenotype also suggests a possible overlap with autism. Neuroserpin could contribute directly at the synapse or through altered neuron migration during early development leading to the "underconnectivity" that underlies autism by potentially contributing to the excess of short connections and not enough long ones seen in autistic brains, possibly due to an imbalance in pruning of neurons and synapses early in life. It is thus proposed to sequence the neuroserpin gene in initially 20, and subsequently up to 100 idiopathic autistic patients selected as having the language impairment and perseveration endophenotypes.
Detailed description
It is proposed to perform a pilot study to ask whether genetic variation at SERPINI1 is contributing to idiopathic autism. To maximize the chance of finding such variants, the perseveration and language delay endophenotypes (simpler intermediate traits) will be used to select twenty autistic multiplex (and if necessary singleplex) families with idiopathic autistic patients who have been evaluated with the Autism Diagnostic Interview-revised (ADI-R) and their nuclear families ( siblings and their parents) will be identified by Dr. Liptak and Dr. Lebel with the assistance of Ms Klausner and recruited. Patients with syndromic autism due to known causes such as fragile X syndrome, Tuberous sclerosis, Down syndrome, and Neurofibromatosis type I will be excluded. The entire SERPINI1 coding region (nine exons), one kilobase of promoter region (Chen, 2007) and at least 200 bp of intron flanking each exon will be sequenced in an index case and the segregation of mutations identified investigated within the families. All mutations that appear to be good functional candidates will be compared in frequency amongst autistic and control populations in order to determine if a case can be made that SERPINI1 could be contributing to autism. In addition, known neuroserpin SNPs identified through the Hapmap project (www.hapmap.org) will be investigated and tested for evidence of transmission distortion/disequilibrium by linkage/association analysis. Depending on the results from this initial experiment it is proposed to subsequently sequence up to a further 80 local autism patients (maximum of 100 patients). Additional studies would be performed as follow up studies to similarly sequence the genes of other serpins expressed in the brain; Plasminogen activator 1, PA1, SERPINE1 located at the MLS linkage peak at 7q22.1 seen in IMGSAC study (Lamb, 2002) while Proteinase nexin 1, PN1 SERPINE2 at 2q36.1,close to previously identified linkage peaks (Autism Genome Project consortium, 2007) and potentially their putative serine protease targets (tPA at 8p11.21 and uPA at 10q22.2) and the upstream neuroserpin activators (ALK6, AMH and BMP2) (Lebeurrier, 2008). tPA expression is increased by events that require synaptic plasticity (Yepes, 2002) and enhances NMDA receptor signaling by cleavage of its NR1 subunit (Pawlack, 2002). All interesting leads will be pursued by obtaining additional samples from the Autism Genetic Resource Exchange (AGRE)( www.agre.org), a publically available recourse of phenotypic data and bio-materials which provides diagnostic information and DNA from 100's of multiplex ASD families.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | – | –Autistic patients. |
| 2 | – | –Matched controls |
Who may qualify
- Ages
- 1 year and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Autistic patients and their first degree relatives
Key inclusion criteria (1 listed)
- Autistic patient, or first degree relative of autistic patient
Key exclusion criteria (1 listed)
- Less than one year of age.
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
Determine SERPIN1 gene sequence variation in autistic subjects.
Time frame: one year
Results and safety
The study was stopped early (reason given: Lack of enrollment.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2016.
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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.
Antony E Shrimpton, PhD principal investigator
State University of New York - Upstate Medical University
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 Autism, run by State University of New York - Upstate Medical University 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 1 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: stopped early, as of the sponsor's last update on 19 Apr 2016. 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 was stopped early (reason given: Lack of enrollment.). Results are not available in the source record.
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?
Determine SERPIN1 gene sequence variation in autistic subjects. (time frame: one year). 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 19 Apr 2016.