Ehlers Danlos SyndromeNCT01367977
Head Circumference Growth in Children With Ehlers-Danlos Syndrome Who Develop Dysautonomia Later in Life
An observational study of Ehlers Danlos Syndrome and External Hydrocephalus, run by Genetic Disease Investigators at 1 site in United States.
Trial summary
It is known that 33-50% of Classic and Hypermobile Ehlers-Danlos Syndrome patients eventually develop dysautonomia, otherwise known as "POTS" (Postural Orthostatic Tachycardia Syndrome). Read more about this study
- Who is it for?
- Ages 5 years and older
- Conditions the study is for
- Ehlers Danlos Syndrome, External Hydrocephalus, Dysautonomia
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- May 2011to Apr 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 5 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients with Classic or Hypermobile Ehlers-Danlos Syndrome with dysautonomia, found through social media forums, internet advertising, local support groups, physicians working with this subset of patients.
Who may be able to join
- Diagnosis, or suspected diagnosis of Classic or Hypermobile Ehlers-Danlos Syndrome and dysautonomia
- Must be able to present their head circumferences, weight and length for the first 15 months of their lives
Who cannot join
- Patients unable to present their head circumferences, weight and length for the first 15 months of their lives
- Patients with dysautonomia due to stroke of the brain stem
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Head Circumference Growth in Children With Ehlers-Danlos Syndrome Who Develop Dysautonomia ("POTS" -- Postural Orthostatic Tachycardia Syndrome)Later in Life -- a Retrospective Analysis
It is known that 33-50% of Classic and Hypermobile Ehlers-Danlos Syndrome patients eventually develop dysautonomia, otherwise known as "POTS" (Postural Orthostatic Tachycardia Syndrome). Some of these patients develop dysautonomia as a result of a retroflexed odontoid, Chiari 1 Malformation or cranial settling and the resulting basilar impression. Many Ehlers-Danlos patients suffer with the same symptomology with no evidence of a cause according to MRI imaging.
It is the author's hypothesis that low-level External Communicating Hydrocephalus appears to be responsible for the constellation of autonomic and cranial nerve symptoms, and if present in the very young, an analysis of head circumference growth in the first 15 months of life should reflect abnormally rapid head growth, supporting this hypothesis.
Read the detailed description
It is known that 33-50% of Classic and Hypermobile Ehlers-Danlos Syndrome patients eventually develop dysautonomia, otherwise known as "POTS" - Postural Orthostatic Tachycardia Syndrome. Some of these patients develop dysautonomia as a result of a retroflexed odontoid, Chiari 1 Malformation or cranial settling and the resulting basilar impression. However, many Ehlers-Danlos patients suffer with the same symptomology with no evidence of cause according to MRI imaging. It is the author's hypothesis that low-level External Communicating Hydrocephalus appears to be responsible for the constellation of autonomic and cranial nerve symptoms, and if present in the very young, an analysis of head circumference growth in the first 15 months of life should reflect abnormally rapid head growth, supporting the hypothesis.
The investigators will evaluate the head circumference of Ehlers-Danlos patients who display dysautonomia later in life. The head circumference analyzed will be from birth to approximately 15 months of age, as the sutures of the skull generally fuse between 16 and 18 months. Additionally, pediatricians do not usually measure head circumference routinely beyond this age.
In a small subset of Ehlers-Danlos patients who developed postural orthostatic tachycardia syndrome in their childhood or teen years, retrospective analysis of their head circumferences indicates such megalocephaly. On average, the children's heads were found to increase from approximately the 35th percentile to over the 90th percentile. Their weights and lengths did not increase in the same fashion, although some of the children remained in the higher percentages for their length.
A review of literature indicates that studies of children with megalocephaly (not necessarily having the diagnosis of Ehlers-Danlos) were considered to have a benign condition ("Benign External Communicating Hydrocephalus") because CT's at the age of 2 or 3 years appeared normal and neurological exams also appeared normal. However, studies have also shown that a large percentage of these children exhibited delayed motor development and some of them had delayed speech development.In some studies these children were treated with Diamox, and in other studies the children were merely observed.
It is the author's hypothesis that delayed motor development found in Ehlers-Danlos children is due at least in part to hydrocephalus, and not merely due to flexible joints, as previously surmised.
It is the author's contention that mild symptoms of irritability, headaches, sleep disorders, emotional "fits", and the later development of dysautonomia were never considered in these studies, yet are the likely symptoms of a low level of pressure that continued to be exerted on the brains of these children.
High pressure on the brain (even if subtle) could be evidence of congenital CCSVI (cerebrospinal venous insufficiency) or increased CSF (cerebral spinal fluid) production, or the poor drainage of cerebral spinal fluid, or both. Retrospective examination of skull expansion is a necessary step to ascertain these possibilities, allowing for early treatment and the hope of avoidance of the neurological symptoms, and often disabling effects of dysautonomia (and/or multiple sclerosis). It is the author's contention that "Benign External Hydrocephalus" is not a benign condition.
- Conditions
- Ehlers Danlos Syndrome, External Hydrocephalus, Dysautonomia, Postural Orthostatic Tachycardia Syndrome, Venous Insufficiency
- Keywords
- Ehlers Danlos Syndrome, External Communicating Hydrocephalus, Dysautonomia, Postural orthostatic tachycardia syndrome, Chronic cerebrospinal venous insufficiency
- Medical subject headings
- Ehlers-Danlos Syndrome, Autonomic Nervous System Diseases, Postural Orthostatic Tachycardia Syndrome, Venous Insufficiency
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 |
|---|---|---|
| Ehlers-Danlos patients | Patients with diagnosed or suspected Classic or Hypermobile Ehlers-Danlos Syndrome |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measurement of Head Circumference in Ehlers-Danlos patients (retrospectively), between the ages of birth to 15 months of age.
Measurements of head circumferences, weight and length of children (retrospectively), will be compared to "normals" as established by the U.S. Department of Health and Human Services, Centers for Disease Control and Prevention (CDC), 2008.
Measured: Retrospectively, between patients' birth to 15 months of age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2011 (estimated)
- Study startMay 2011
- Primary completionApr 2015
- Study completionApr 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Ehlers Danlos 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 only
- Time perspective
- Retrospective
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genetic Disease Investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Diana L Driscoll, O.D., Principal investigator, Genetic Disease Investigators
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01367977
- Sponsor's protocol ID
- 61/3528
- Status last verified
- Apr 2015
- First submitted
- 5 Jun 2011
- Last updated
- 14 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Alvarez LA, Maytal J, Shinnar S. Idiopathic external hydrocephalus: natural history and relationship to benign familial macrocephaly. Pediatrics. 1986 Jun;77(6):901-7.
PubMed 3714384Hakim A. Hypermobile Ehlers-Danlos Syndrome. 2004 Oct 22 [updated 2024 Feb 22]. In: Adam MP, Bick S, Mirzaa GM, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK1279/
PubMed 20301456Milhorat TH, Bolognese PA, Nishikawa M, McDonnell NB, Francomano CA. Syndrome of occipitoatlantoaxial hypermobility, cranial settling, and chiari malformation type I in patients with hereditary disorders of connective tissue. J Neurosurg Spine. 2007 Dec;7(6):601-9. doi: 10.3171/SPI-07/12/601.
PubMed 18074684Kumar R. External hydrocephalus in small children. Childs Nerv Syst. 2006 Oct;22(10):1237-41. doi: 10.1007/s00381-006-0047-1. Epub 2006 Mar 23.
PubMed 16555081
Study at a glance
From the registry record, last updated by the sponsor on 14 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Head Circumference Growth in Children With Ehlers-Danlos Syndrome Who Develop Dysautonomia ("POTS" -- Postural Orthostatic Tachycardia Syndrome)Later in Life -- a Retrospective Analysis
- ClinicalTrials.gov ID
- NCT01367977
- Acronym / sponsor ID
- 61/3528
- Conditions
- Ehlers Danlos Syndrome, External Hydrocephalus, Dysautonomia, Postural Orthostatic Tachycardia Syndrome, Venous Insufficiency
- Keywords
- Ehlers Danlos Syndrome, External Communicating Hydrocephalus, Dysautonomia, Postural orthostatic tachycardia syndrome, Chronic cerebrospinal venous insufficiency
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Genetic Disease InvestigatorsUniversity, hospital or other
- Study start
- May 2011
- Primary completion
- Apr 2015 (actual)
- Study completion
- Apr 2015 (actual)
- First posted
- 7 Jun 2011 (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.
It is known that 33-50% of Classic and Hypermobile Ehlers-Danlos Syndrome patients eventually develop dysautonomia, otherwise known as "POTS" (Postural Orthostatic Tachycardia Syndrome). Some of these patients develop dysautonomia as a result of a retroflexed odontoid, Chiari 1 Malformation or cranial settling and the resulting basilar impression. Many Ehlers-Danlos patients suffer with the same symptomology with no evidence of a cause according to MRI imaging.
It is the author's hypothesis that low-level External Communicating Hydrocephalus appears to be responsible for the constellation of autonomic and cranial nerve symptoms, and if present in the very young, an analysis of head circumference growth in the first 15 months of life should reflect abnormally rapid head growth, supporting this hypothesis.
Detailed description
It is known that 33-50% of Classic and Hypermobile Ehlers-Danlos Syndrome patients eventually develop dysautonomia, otherwise known as "POTS" - Postural Orthostatic Tachycardia Syndrome. Some of these patients develop dysautonomia as a result of a retroflexed odontoid, Chiari 1 Malformation or cranial settling and the resulting basilar impression. However, many Ehlers-Danlos patients suffer with the same symptomology with no evidence of cause according to MRI imaging. It is the author's hypothesis that low-level External Communicating Hydrocephalus appears to be responsible for the constellation of autonomic and cranial nerve symptoms, and if present in the very young, an analysis of head circumference growth in the first 15 months of life should reflect abnormally rapid head growth, supporting the hypothesis.
The investigators will evaluate the head circumference of Ehlers-Danlos patients who display dysautonomia later in life. The head circumference analyzed will be from birth to approximately 15 months of age, as the sutures of the skull generally fuse between 16 and 18 months. Additionally, pediatricians do not usually measure head circumference routinely beyond this age.
In a small subset of Ehlers-Danlos patients who developed postural orthostatic tachycardia syndrome in their childhood or teen years, retrospective analysis of their head circumferences indicates such megalocephaly. On average, the children's heads were found to increase from approximately the 35th percentile to over the 90th percentile. Their weights and lengths did not increase in the same fashion, although some of the children remained in the higher percentages for their length.
A review of literature indicates that studies of children with megalocephaly (not necessarily having the diagnosis of Ehlers-Danlos) were considered to have a benign condition ("Benign External Communicating Hydrocephalus") because CT's at the age of 2 or 3 years appeared normal and neurological exams also appeared normal. However, studies have also shown that a large percentage of these children exhibited delayed motor development and some of them had delayed speech development.In some studies these children were treated with Diamox, and in other studies the children were merely observed.
It is the author's hypothesis that delayed motor development found in Ehlers-Danlos children is due at least in part to hydrocephalus, and not merely due to flexible joints, as previously surmised.
It is the author's contention that mild symptoms of irritability, headaches, sleep disorders, emotional "fits", and the later development of dysautonomia were never considered in these studies, yet are the likely symptoms of a low level of pressure that continued to be exerted on the brains of these children.
High pressure on the brain (even if subtle) could be evidence of congenital CCSVI (cerebrospinal venous insufficiency) or increased CSF (cerebral spinal fluid) production, or the poor drainage of cerebral spinal fluid, or both. Retrospective examination of skull expansion is a necessary step to ascertain these possibilities, allowing for early treatment and the hope of avoidance of the neurological symptoms, and often disabling effects of dysautonomia (and/or multiple sclerosis). It is the author's contention that "Benign External Hydrocephalus" is not a benign condition.
Study design
- Observational model
- Case only
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ehlers-Danlos patients | – | –Patients with diagnosed or suspected Classic or Hypermobile Ehlers-Danlos Syndrome |
Who may qualify
- Ages
- 5 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients with Classic or Hypermobile Ehlers-Danlos Syndrome with dysautonomia, found through social media forums, internet advertising, local support groups, physicians working with this subset of patients.
Key inclusion criteria (2 listed)
- Diagnosis, or suspected diagnosis of Classic or Hypermobile Ehlers-Danlos Syndrome and dysautonomia
- Must be able to present their head circumferences, weight and length for the first 15 months of their lives
Key exclusion criteria (2 listed)
- Patients unable to present their head circumferences, weight and length for the first 15 months of their lives
- Patients with dysautonomia due to stroke of the brain stem
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
Measurement of Head Circumference in Ehlers-Danlos patients (retrospectively), between the ages of birth to 15 months of age.
Time frame: Retrospectively, between patients' birth to 15 months of age
Measurements of head circumferences, weight and length of children (retrospectively), will be compared to "normals" as established by the U.S. Department of Health and Human Services, Centers for Disease Control and Prevention (CDC), 2008.
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 14 Feb 2024.
- Background: PubMed 3714384Alvarez LA, Maytal J, Shinnar S. Idiopathic external hydrocephalus: natural history and relationship to benign familial macrocephaly. Pediatrics. 1986 Jun;77(6):901-7.
- Background: PubMed 20301456Hakim A. Hypermobile Ehlers-Danlos Syndrome. 2004 Oct 22 [updated 2024 Feb 22]. In: Adam MP, Bick S, Mirzaa GM, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK1279/
- Background: PubMed 18074684Milhorat TH, Bolognese PA, Nishikawa M, McDonnell NB, Francomano CA. Syndrome of occipitoatlantoaxial hypermobility, cranial settling, and chiari malformation type I in patients with hereditary disorders of connective tissue. J Neurosurg Spine. 2007 Dec;7(6):601-9. doi: 10.3171/SPI-07/12/601.
- Background: PubMed 16555081Kumar R. External hydrocephalus in small children. Childs Nerv Syst. 2006 Oct;22(10):1237-41. doi: 10.1007/s00381-006-0047-1. Epub 2006 Mar 23.
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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.
Diana L Driscoll, O.D. principal investigator
Genetic Disease Investigators
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 Ehlers Danlos Syndrome and External Hydrocephalus, run by Genetic Disease Investigators 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 2 inclusion and 2 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 14 Feb 2024. 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?
Measurement of Head Circumference in Ehlers-Danlos patients (retrospectively), between the ages of birth to 15 months of age. (time frame: Retrospectively, between patients' birth to 15 months of age). 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 NCT01367977, which also lists 4 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 14 Feb 2024.