Autism Spectrum DisorderNCT03152838
The Role of Epigenetic Modifications in Autism Spectrum Disorder
An observational study of Autism Spectrum Disorder, run by Assiut University.
Trial summary
Autism Spectrum Disorder is a neurodevelopmental disorder characterized by impaired social communication and repetitive or stereotyped behaviors. According to the World Health Organization , the prevalence of Autism Spectrum Disorder is one person in 160. Read more about this study
- Who is it for?
- Ages 2 to 6 years
- Conditions the study is for
- Autism Spectrum Disorder
- What is being tested?
- DNA methylation and Real-time Polymerase Chain Reaction Analysis and Gilliam Autism Rating Scale Arabic version
- How many people
- 40 participants
- Where
- No sites listed yet
- Study dates
- 1 Sep 2017to 1 Mar 2019
- 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 2 to 6 years
- All sexes
- Child
Study population: The children attending the pediatric clinic at Assiut University Hospital
Who may be able to join
- - All enrolled children with Autism Spectrum Disorder will be:
- Exhibit symptoms within the typical triad of autistic traits: communication impairment, social deficits, and ritualistic interests.
- Drug-naïve.
- Children with Autism Spectrum Disorder and controls will be 2-6 years old.
Who cannot join
- The control subjects will also clinically examined by the psychiatrist to exclude any sub-clinical autistic features. Children with Autism Spectrum Disorder and controls will excluded from the study if
- They receive treatment for any reason.
- -Endocrinological disease, mental retardation, communication disorder, psychotic disorder, attention deficit hyperactivity disorder and learning disorders seen in the children or their family members.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: The Role of Epigenetic Modifications in Autism Spectrum Disorder Through DNA Methylation
Autism Spectrum Disorder is a neurodevelopmental disorder characterized by impaired social communication and repetitive or stereotyped behaviors. According to the World Health Organization , the prevalence of Autism Spectrum Disorder is one person in 160.
Read the detailed description
Genetic and non-genetic factors would contribute to the development of autism. However, the molecular mechanisms of ASD are not clear and successful treatments are still under research. Autism Spectrum Disorder can occur due to exposure to environmental pollutants which lead to epigenetic changes like DNA methylation, acetylation and post-translational modifications. However, the role of epigenetic changes in Autism Spectrum Disorder is still debated.
Epigenetic mechanisms represent a link through which environmental factors interact with the genetic factors resulting in modification of Autism Spectrum Disorder risk through changes in gene expression. DNA methylation and histone deacetylation are two major epigenetic mechanisms that regulate the gene expression at successive stages of brain development.
Brain derived neurotrophic factor is responsible for brain development. Altered BDNF levels and expression may be closely associated with Autism Spectrum Disorder. . Glial fibrillary acidic protein is the hallmark intermediate filament protein in astrocytes, the main type of glial cells in the central nervous system. Interestingly, Glial fibrillary acidic protein is a marker of astroglial activation and the recent data indicated that Glial fibrillary acidic protein could be implicated in the pathophysiology of autism. However, the underlying mechanisms for the role of brain derived neurotrophic factor and glial fibrillary acidic protein in autism spectrum disorder are poorly understood.
- Conditions
- Autism Spectrum Disorder
- Being tested
- DNA methylation and Real-time Polymerase Chain Reaction Analysis, Gilliam Autism Rating Scale Arabic version
- Medical subject headings
- Autism Spectrum Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DNA methylation and Real-time Polymerase Chain Reaction AnalysisGenetic
Fasting blood samples will be collected from both autism and controls for DNA extraction. Peripheral blood (2ml) will be drawn from the cubital vein intoplastic syringes. Lymphocytes will be isolated from blood samples. We will examine the gene methylation in the peripheral blood lymphocytes of drug-naı¨ve autism patients and control subjects.
DNA will be isolated from lymphocytes, purified and processed for bisulfate modification. Bisulfate treatment of genomic DNA will be performed using DNA methylation kit according to the manufacturer´ instructions. Bisulfite treatment of genomic DNA converts cytosine to uracil, but leaves methylated 5'Cytosines unchanged. Quantitative real time Polymerase chain reaction will be used to determine the DNA methylation status of the Brian derived neurotrophic factor and glia fibrillary acidic protein genes using primers specific to the human genes.
Gilliam Autism Rating Scale Arabic versionDiagnostic test
An assessment of the severity of autism using the Gilliam autism rating scale Arabic version: This test was used for diagnosis and assessment of the severity of autistic features for ages 3-22 years. It consists of 56 items, subdivided into 4 subscales: communication, social interaction, stereotyped behaviors, development and total score. The Arabic version has been validated with good reliability and validity and used in many studies before. The lower the scores are, the worse the condition is.
The scale will be done by trained and certified psychologist. The protocol and informed consent for this study will be reviewed and approved by the ethics committee at the Faculty of Medicine, Assiut University, Egypt.
| Study group | Role | What they receive |
|---|---|---|
| Autism Cases | 20 confirmed autism cases will be involved in this study.
1. The autism patients will be diagnosed according to:Gilliam Autism Rating Scale Arabic version: An assessment of the severity of autism using the Gilliam autism rating scale Arabic version: This test was used for diagnosis and assessment of the severity of autistic features for ages 3-22 years. It consists of 56 items, subdivided into 4 subscales: communication, social interaction, stereotyped behaviors, development and total score.
2. Fasting blood samples will be collected from autism children for DNA Methylation-and quantitative Real-time Polymerase Chain Reaction Analysis Receives: Genetic: DNA methylation and Real-time Polymerase Chain Reaction Analysis; Diagnostic Test: Gilliam Autism Rating Scale Arabic version | |
| Control | 20 age-gender matched typical development children that will be assigned to the normal control group.
1. Control children will be examined by a psychiatrist to exclude any sub-clinical autistic features.
2. Fasting blood samples will be collected from control children for DNA Methylation-and quantitative Real-time Polymerase Chain Reaction Analysis Receives: Genetic: DNA methylation and Real-time Polymerase Chain Reaction Analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
The difference of percentage of DNA methylation of Brain derived neurotrophic factor gene and glial fibrillary acidic protein gene between the two groups
Real Time Polymerase Chain Reaction
Measured: one year
The relation between the severity of autistic symptoms and percentage of Brain derived neurotrophic factor gene and glial fibrillary acidic protein gene methylation in Autism cases group
correlation test
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 posted15 May 2017
- Study start1 Sep 2017 (estimated)
- Primary completion1 Sep 2018 (estimated)
- Study completion1 Mar 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Autism Spectrum DisorderStudies of the same condition, open and under way.
- More trials run by Assiut UniversityThe sponsor's other registered studies.
- 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
- Retrospective
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rasha Mohammed Ali, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03152838
- Sponsor's protocol ID
- HRM
- Status last verified
- May 2017
- First submitted
- 12 May 2017
- Last updated
- 15 May 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Bahi A. Sustained lentiviral-mediated overexpression of microRNA124a in the dentate gyrus exacerbates anxiety- and autism-like behaviors associated with neonatal isolation in rats. Behav Brain Res. 2016 Sep 15;311:298-308. doi: 10.1016/j.bbr.2016.05.033. Epub 2016 May 17.
PubMed 27211062Bhandari R, Kuhad A. Resveratrol suppresses neuroinflammation in the experimental paradigm of autism spectrum disorders. Neurochem Int. 2017 Feb;103:8-23. doi: 10.1016/j.neuint.2016.12.012. Epub 2016 Dec 23.
PubMed 28025035Gladkevich A, Kauffman HF, Korf J. Lymphocytes as a neural probe: potential for studying psychiatric disorders. Prog Neuropsychopharmacol Biol Psychiatry. 2004 May;28(3):559-76. doi: 10.1016/j.pnpbp.2004.01.009.
PubMed 15093964Paternain L, Martisova E, Campion J, Martinez JA, Ramirez MJ, Milagro FI. Methyl donor supplementation in rats reverses the deleterious effect of maternal separation on depression-like behaviour. Behav Brain Res. 2016 Feb 15;299:51-8. doi: 10.1016/j.bbr.2015.11.031. Epub 2015 Nov 25.
PubMed 26628207Vuong HE, Hsiao EY. Emerging Roles for the Gut Microbiome in Autism Spectrum Disorder. Biol Psychiatry. 2017 Mar 1;81(5):411-423. doi: 10.1016/j.biopsych.2016.08.024. Epub 2016 Aug 26.
PubMed 27773355Wang J, Zou Q, Han R, Li Y, Wang Y. Serum levels of Glial fibrillary acidic protein in Chinese children with autism spectrum disorders. Int J Dev Neurosci. 2017 Apr;57:41-45. doi: 10.1016/j.ijdevneu.2017.01.004. Epub 2017 Jan 11.
PubMed 28088366Nishimura K, Nakamura K, Anitha A, Yamada K, Tsujii M, Iwayama Y, Hattori E, Toyota T, Takei N, Miyachi T, Iwata Y, Suzuki K, Matsuzaki H, Kawai M, Sekine Y, Tsuchiya K, Sugihara G, Suda S, Ouchi Y, Sugiyama T, Yoshikawa T, Mori N. Genetic analyses of the brain-derived neurotrophic factor (BDNF) gene in autism. Biochem Biophys Res Commun. 2007 Apr 27;356(1):200-6. doi: 10.1016/j.bbrc.2007.02.135. Epub 2007 Mar 5.
PubMed 17349978Ferreira MC, Dorboz I, Rodriguez D, Boespflug Tanguy O. Screening for GFAP rearrangements in a cohort of Alexander disease and undetermined leukoencephalopathy patients. Eur J Med Genet. 2015 Sep;58(9):466-70. doi: 10.1016/j.ejmg.2015.07.002. Epub 2015 Jul 21.
PubMed 26208460Samadi SA, McConkey R. The utility of the Gilliam autism rating scale for identifying Iranian children with autism. Disabil Rehabil. 2014;36(6):452-6. doi: 10.3109/09638288.2013.797514. Epub 2013 Jun 5.
PubMed 23738615
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Epigenetic Modifications in Autism Spectrum Disorder Through DNA Methylation
- ClinicalTrials.gov ID
- NCT03152838
- Acronym / sponsor ID
- HRM
- Conditions
- Autism Spectrum Disorder
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- 1 Sep 2017 (estimated)
- Primary completion
- 1 Sep 2018 (estimated)
- Study completion
- 1 Mar 2019 (estimated)
- First posted
- 15 May 2017 (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.
Autism Spectrum Disorder is a neurodevelopmental disorder characterized by impaired social communication and repetitive or stereotyped behaviors. According to the World Health Organization , the prevalence of Autism Spectrum Disorder is one person in 160.
Detailed description
Genetic and non-genetic factors would contribute to the development of autism. However, the molecular mechanisms of ASD are not clear and successful treatments are still under research. Autism Spectrum Disorder can occur due to exposure to environmental pollutants which lead to epigenetic changes like DNA methylation, acetylation and post-translational modifications. However, the role of epigenetic changes in Autism Spectrum Disorder is still debated.
Epigenetic mechanisms represent a link through which environmental factors interact with the genetic factors resulting in modification of Autism Spectrum Disorder risk through changes in gene expression. DNA methylation and histone deacetylation are two major epigenetic mechanisms that regulate the gene expression at successive stages of brain development.
Brain derived neurotrophic factor is responsible for brain development. Altered BDNF levels and expression may be closely associated with Autism Spectrum Disorder. . Glial fibrillary acidic protein is the hallmark intermediate filament protein in astrocytes, the main type of glial cells in the central nervous system. Interestingly, Glial fibrillary acidic protein is a marker of astroglial activation and the recent data indicated that Glial fibrillary acidic protein could be implicated in the pathophysiology of autism. However, the underlying mechanisms for the role of brain derived neurotrophic factor and glial fibrillary acidic protein in autism spectrum disorder are poorly understood.
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Autism Cases | – | Genetic: DNA methylation and Real-time Polymerase Chain Reaction Analysis, Diagnostic Test: Gilliam Autism Rating Scale Arabic version20 confirmed autism cases will be involved in this study. 1. The autism patients will be diagnosed according to:Gilliam Autism Rating Scale Arabic version: An assessment of the severity of autism using the Gilliam autism rating scale Arabic version: This test was used for diagnosis and assessment of the severity of autistic features for ages 3-22 years. It consists of 56 items, subdivided into 4 subscales: communication, social interaction, stereotyped behaviors, development and total score. 2. Fasting blood samples will be collected from autism children for DNA Methylation-and quantitative Real-time Polymerase Chain Reaction Analysis |
| Control | – | Genetic: DNA methylation and Real-time Polymerase Chain Reaction Analysis20 age-gender matched typical development children that will be assigned to the normal control group. 1. Control children will be examined by a psychiatrist to exclude any sub-clinical autistic features. 2. Fasting blood samples will be collected from control children for DNA Methylation-and quantitative Real-time Polymerase Chain Reaction Analysis |
Who may qualify
- Ages
- 2 to 6 years
- Sex
- All
- Age groups
- Child
- Study population
- The children attending the pediatric clinic at Assiut University Hospital
Key inclusion criteria (4 listed)
- - All enrolled children with Autism Spectrum Disorder will be:
- Children with Autism Spectrum Disorder and controls will be 2-6 years old.
Key exclusion criteria (3 listed)
- The control subjects will also clinically examined by the psychiatrist to exclude any sub-clinical autistic features. Children with Autism Spectrum Disorder and controls will excluded from the study if
- They receive treatment for any reason.
- -Endocrinological disease, mental retardation, communication disorder, psychotic disorder, attention deficit hyperactivity disorder and learning disorders seen in the children or their family members.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DNA methylation and Real-time Polymerase Chain Reaction AnalysisFasting blood samples will be collected from both autism and controls for DNA extraction. Peripheral blood (2ml) will be drawn from the cubital vein intoplastic syringes. Lymphocytes will be isolated from blood samples. We will examine the gene methylation in the peripheral blood lymphocytes of drug-naı¨ve autism patients and control subjects. DNA will be isolated from lymphocytes, purified and processed for bisulfate modification. Bisulfate treatment of genomic DNA will be performed using DNA methylation kit according to the manufacturer´ instructions. Bisulfite treatment of genomic DNA converts cytosine to uracil, but leaves methylated 5'Cytosines unchanged. Quantitative real time Polymerase chain reaction will be used to determine the DNA methylation status of the Brian derived neurotrophic factor and glia fibrillary acidic protein genes using primers specific to the human genes. | Genetic | Autism Cases, Control |
| Gilliam Autism Rating Scale Arabic versionAn assessment of the severity of autism using the Gilliam autism rating scale Arabic version: This test was used for diagnosis and assessment of the severity of autistic features for ages 3-22 years. It consists of 56 items, subdivided into 4 subscales: communication, social interaction, stereotyped behaviors, development and total score. The Arabic version has been validated with good reliability and validity and used in many studies before. The lower the scores are, the worse the condition is. The scale will be done by trained and certified psychologist. The protocol and informed consent for this study will be reviewed and approved by the ethics committee at the Faculty of Medicine, Assiut University, Egypt. | Diagnostic test | Autism Cases |
Primary outcome
The difference of percentage of DNA methylation of Brain derived neurotrophic factor gene and glial fibrillary acidic protein gene between the two groups
Time frame: one year
Real Time Polymerase Chain Reaction
The relation between the severity of autistic symptoms and percentage of Brain derived neurotrophic factor gene and glial fibrillary acidic protein gene methylation in Autism cases group
Time frame: one year
correlation test
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2017.
- Results publication: PubMed 27211062Bahi A. Sustained lentiviral-mediated overexpression of microRNA124a in the dentate gyrus exacerbates anxiety- and autism-like behaviors associated with neonatal isolation in rats. Behav Brain Res. 2016 Sep 15;311:298-308. doi: 10.1016/j.bbr.2016.05.033. Epub 2016 May 17.
- Results publication: PubMed 28025035Bhandari R, Kuhad A. Resveratrol suppresses neuroinflammation in the experimental paradigm of autism spectrum disorders. Neurochem Int. 2017 Feb;103:8-23. doi: 10.1016/j.neuint.2016.12.012. Epub 2016 Dec 23.
- Results publication: PubMed 15093964Gladkevich A, Kauffman HF, Korf J. Lymphocytes as a neural probe: potential for studying psychiatric disorders. Prog Neuropsychopharmacol Biol Psychiatry. 2004 May;28(3):559-76. doi: 10.1016/j.pnpbp.2004.01.009.
- Results publication: PubMed 26628207Paternain L, Martisova E, Campion J, Martinez JA, Ramirez MJ, Milagro FI. Methyl donor supplementation in rats reverses the deleterious effect of maternal separation on depression-like behaviour. Behav Brain Res. 2016 Feb 15;299:51-8. doi: 10.1016/j.bbr.2015.11.031. Epub 2015 Nov 25.
- Results publication: PubMed 27773355Vuong HE, Hsiao EY. Emerging Roles for the Gut Microbiome in Autism Spectrum Disorder. Biol Psychiatry. 2017 Mar 1;81(5):411-423. doi: 10.1016/j.biopsych.2016.08.024. Epub 2016 Aug 26.
- Results publication: PubMed 28088366Wang J, Zou Q, Han R, Li Y, Wang Y. Serum levels of Glial fibrillary acidic protein in Chinese children with autism spectrum disorders. Int J Dev Neurosci. 2017 Apr;57:41-45. doi: 10.1016/j.ijdevneu.2017.01.004. Epub 2017 Jan 11.
- Results publication: PubMed 17349978Nishimura K, Nakamura K, Anitha A, Yamada K, Tsujii M, Iwayama Y, Hattori E, Toyota T, Takei N, Miyachi T, Iwata Y, Suzuki K, Matsuzaki H, Kawai M, Sekine Y, Tsuchiya K, Sugihara G, Suda S, Ouchi Y, Sugiyama T, Yoshikawa T, Mori N. Genetic analyses of the brain-derived neurotrophic factor (BDNF) gene in autism. Biochem Biophys Res Commun. 2007 Apr 27;356(1):200-6. doi: 10.1016/j.bbrc.2007.02.135. Epub 2007 Mar 5.
- Results publication: PubMed 26208460Ferreira MC, Dorboz I, Rodriguez D, Boespflug Tanguy O. Screening for GFAP rearrangements in a cohort of Alexander disease and undetermined leukoencephalopathy patients. Eur J Med Genet. 2015 Sep;58(9):466-70. doi: 10.1016/j.ejmg.2015.07.002. Epub 2015 Jul 21.
- Results publication: PubMed 23738615Samadi SA, McConkey R. The utility of the Gilliam autism rating scale for identifying Iranian children with autism. Disabil Rehabil. 2014;36(6):452-6. doi: 10.3109/09638288.2013.797514. Epub 2013 Jun 5.
- Individual participant dataSharing planned: No
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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.
Questions about this trial
What is this clinical trial studying?
An observational study of Autism Spectrum Disorder, run by Assiut University.
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 4 inclusion and 3 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: status not confirmed, as of the sponsor's last update on 15 May 2017. Status can change between updates, so confirm with the study contact before making plans.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Omyma Galal, MD (01006807029, omyma_galal@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The difference of percentage of DNA methylation of Brain derived neurotrophic factor gene and glial fibrillary acidic protein gene between the two groups (time frame: one year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03152838, which also lists 9 linked publications.
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 15 May 2017.