Smith-Lemli-Opitz SyndromePhase 1/2NCT00272844
Treatment of the Cholesterol Defect in Smith-Lemli-Opitz Syndrome
A Phase 1/2 study testing crystalline cholesterol oil-based suspension in people with Smith-Lemli-Opitz Syndrome, run by Boston Children's Hospital at 1 site in United States.
Trial summary
The purpose of this study is to determine whether supplementation with an oil-based cholesterol suspension will correct the biochemical abnormalities in cholesterol and its precursors in individuals with the Smith-Lemli-Opitz syndrome. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Smith-Lemli-Opitz Syndrome
- What is being tested?
- crystalline cholesterol oil-based suspension
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 1998to Jul 2011
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Biochemical confirmation of sterol defect associated with Smith-Lemli-Opitz syndrome
Who cannot join
- Inability to tolerate crystalline cholesterol
- Inability to travel to Boston 3-4 times/year based on age
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital Boston
Boston, Massachusetts, 02115
About this study
The purpose of this study is to determine whether supplementation with an oil-based cholesterol suspension will correct the biochemical abnormalities in cholesterol and its precursors in individuals with the Smith-Lemli-Opitz syndrome.
Read the detailed description
This study involves treating individuals with the Smith-Lemli-Opitz syndrome, a rare inborn error of cholesterol metabolism, with supplemental cholesterol to determine it effects on biochemical sterol metabolites, growth, neuropsychological development, ophthalmologic and auditory function, ERG (electroretinogram) parameters, and CNS metabolites as determined by brain MRS-imaging. Safety of the supplemental cholesterol suspension is monitored by tests of hematologic, renal, and liver function at periodic intervals. There is also a substudy that is investigating potential genotype-phenotype correlations, as well as another that studies biochemical parameters of light sensitivity in cultured skin fibroblasts from affected patients.
- Conditions
- Smith-Lemli-Opitz Syndrome
- Being tested
- crystalline cholesterol oil-based suspension
- Keywords
- cholesterol, Smith-Lemli-Opitz syndrome, mental retardation, sterols, congenital anomalies
- Medical subject headings
- Smith-Lemli-Opitz Syndrome, Intellectual Disability, Congenital Abnormalities
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
crystalline cholesterol oil-based suspensionDrug
200 mg/mL suspension of crystalline cholesterol in oil. Dosage (generally 75-300 mg/kg/day in divided doses) is based on initial cholesterol levels and regulated to increase, yet maintain, cholesterol levels no higher than normal ranges.
| Study group | Role | What they receive |
|---|---|---|
| Cholesterol supplementation | Experimental | Not described Receives: Drug: crystalline cholesterol oil-based suspension |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Responders
Responders was defined as an increase in total serum cholesterol and a decrease in 7-DHC (7-Dehydrocholesterol), and 8-DHC (8-Dehydrocholesterol) were measured on all participants.
Measured: Every 3-6 months for an approximate median of 5 years
Secondary outcomes (2)
Number of Growth Responders
Growth response was defined as an increase in general health, growth, and behavior.
Measured: Every 3-6 months for an approximate median of 5 years
Number of Participants With Improved Neuropsychological Development
Improved neuropsychological development is defined as progressively achieving developmental milestones
Measured: Every 3-6 months for an approximate median of 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2006 (estimated)
- Study startJan 1998
- Primary completionJun 2011
- Study completionJul 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Smith-Lemli-Opitz SyndromeStudies of the same condition, open and under way.
- More trials run by Boston Children's HospitalThe 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
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boston Children's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mira Irons, Boston Children's Hospital
- Investigators
- Mira Irons, M.D., Principal investigator, Boston Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00272844
- Sponsor's protocol ID
- 03-11-189R
- Status last verified
- Sep 2017
- First submitted
- 4 Jan 2006
- Last updated
- 20 Oct 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Irons M, Elias ER, Tint GS, Salen G, Frieden R, Buie TM, Ampola M. Abnormal cholesterol metabolism in the Smith-Lemli-Opitz syndrome: report of clinical and biochemical findings in four patients and treatment in one patient. Am J Med Genet. 1994 May 1;50(4):347-52. doi: 10.1002/ajmg.1320500409.
PubMed 8209913Elias ER, Irons MB, Hurley AD, Tint GS, Salen G. Clinical effects of cholesterol supplementation in six patients with the Smith-Lemli-Opitz syndrome (SLOS). Am J Med Genet. 1997 Jan 31;68(3):305-10. doi: 10.1002/(sici)1096-8628(19970131)68:33.0.co;2-x.
PubMed 9024564Irons M, Elias ER, Abuelo D, Bull MJ, Greene CL, Johnson VP, Keppen L, Schanen C, Tint GS, Salen G. Treatment of Smith-Lemli-Opitz syndrome: results of a multicenter trial. Am J Med Genet. 1997 Jan 31;68(3):311-4.
PubMed 9024565Caruso PA, Poussaint TY, Tzika AA, Zurakowski D, Astrakas LG, Elias ER, Bay C, Irons MB. MRI and 1H MRS findings in Smith-Lemli-Opitz syndrome. Neuroradiology. 2004 Jan;46(1):3-14. doi: 10.1007/s00234-003-1110-1. Epub 2003 Nov 5.
PubMed 14605787Elias ER, Hansen RM, Irons M, Quinn NB, Fulton AB. Rod photoreceptor responses in children with Smith-Lemli-Opitz syndrome. Arch Ophthalmol. 2003 Dec;121(12):1738-43. doi: 10.1001/archopht.121.12.1738.
PubMed 14662594
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of the Cholesterol Defect in Smith-Lemli-Opitz Syndrome
- ClinicalTrials.gov ID
- NCT00272844
- Acronym / sponsor ID
- 03-11-189R
- Conditions
- Smith-Lemli-Opitz Syndrome
- Keywords
- cholesterol, Smith-Lemli-Opitz syndrome, mental retardation, sterols, congenital anomalies
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Boston Children's HospitalUniversity, hospital or other
- Study start
- Jan 1998
- Primary completion
- Jun 2011 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 9 Jan 2006 (estimated)
- Results
- Posted 20 Oct 2017
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 supplementation with an oil-based cholesterol suspension will correct the biochemical abnormalities in cholesterol and its precursors in individuals with the Smith-Lemli-Opitz syndrome.
Detailed description
This study involves treating individuals with the Smith-Lemli-Opitz syndrome, a rare inborn error of cholesterol metabolism, with supplemental cholesterol to determine it effects on biochemical sterol metabolites, growth, neuropsychological development, ophthalmologic and auditory function, ERG (electroretinogram) parameters, and CNS metabolites as determined by brain MRS-imaging. Safety of the supplemental cholesterol suspension is monitored by tests of hematologic, renal, and liver function at periodic intervals. There is also a substudy that is investigating potential genotype-phenotype correlations, as well as another that studies biochemical parameters of light sensitivity in cultured skin fibroblasts from affected patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cholesterol supplementation | Experimental | Drug: crystalline cholesterol oil-based suspension |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- Biochemical confirmation of sterol defect associated with Smith-Lemli-Opitz syndrome
Key exclusion criteria (2 listed)
- Inability to tolerate crystalline cholesterol
- Inability to travel to Boston 3-4 times/year based on age
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 |
|---|---|---|
| crystalline cholesterol oil-based suspension200 mg/mL suspension of crystalline cholesterol in oil. Dosage (generally 75-300 mg/kg/day in divided doses) is based on initial cholesterol levels and regulated to increase, yet maintain, cholesterol levels no higher than normal ranges. | Drug | Cholesterol supplementation |
Primary outcome
Number of Responders
Time frame: Every 3-6 months for an approximate median of 5 years
Responders was defined as an increase in total serum cholesterol and a decrease in 7-DHC (7-Dehydrocholesterol), and 8-DHC (8-Dehydrocholesterol) were measured on all participants.
2 secondary outcomes
Number of Growth Responders
Time frame: Every 3-6 months for an approximate median of 5 years
Number of Participants With Improved Neuropsychological Development
Time frame: Every 3-6 months for an approximate median of 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 8209913Irons M, Elias ER, Tint GS, Salen G, Frieden R, Buie TM, Ampola M. Abnormal cholesterol metabolism in the Smith-Lemli-Opitz syndrome: report of clinical and biochemical findings in four patients and treatment in one patient. Am J Med Genet. 1994 May 1;50(4):347-52. doi: 10.1002/ajmg.1320500409.
- Results publication: PubMed 9024564Elias ER, Irons MB, Hurley AD, Tint GS, Salen G. Clinical effects of cholesterol supplementation in six patients with the Smith-Lemli-Opitz syndrome (SLOS). Am J Med Genet. 1997 Jan 31;68(3):305-10. doi: 10.1002/(sici)1096-8628(19970131)68:33.0.co;2-x.
- Results publication: PubMed 9024565Irons M, Elias ER, Abuelo D, Bull MJ, Greene CL, Johnson VP, Keppen L, Schanen C, Tint GS, Salen G. Treatment of Smith-Lemli-Opitz syndrome: results of a multicenter trial. Am J Med Genet. 1997 Jan 31;68(3):311-4.
- Results publication: PubMed 14605787Caruso PA, Poussaint TY, Tzika AA, Zurakowski D, Astrakas LG, Elias ER, Bay C, Irons MB. MRI and 1H MRS findings in Smith-Lemli-Opitz syndrome. Neuroradiology. 2004 Jan;46(1):3-14. doi: 10.1007/s00234-003-1110-1. Epub 2003 Nov 5.
- Results publication: PubMed 14662594Elias ER, Hansen RM, Irons M, Quinn NB, Fulton AB. Rod photoreceptor responses in children with Smith-Lemli-Opitz syndrome. Arch Ophthalmol. 2003 Dec;121(12):1738-43. doi: 10.1001/archopht.121.12.1738.
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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.
Mira Irons, M.D. principal investigator
Boston Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing crystalline cholesterol oil-based suspension in people with Smith-Lemli-Opitz Syndrome, run by Boston Children's Hospital 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 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 20 Oct 2017. 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.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Oct 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Responders (time frame: Every 3-6 months for an approximate median of 5 years). 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 NCT00272844, which also lists 5 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 20 Oct 2017.