Sjogren-Larsson Syndrome (SLS)SLSNCT01971957
Sjogren-Larsson Syndrome: Natural History, Clinical Variation and Evaluation of Biochemical Markers
An observational study of Sjogren-Larsson Syndrome (SLS), run by University of Nebraska at 2 sites in United States.
Trial summary
Sjogren-Larsson syndrome (SLS) is a rare genetic disease in which patients typically exhibit ichthyosis (dry, scaly skin), intellectual disability, spasticity, seizures and a distinctive maculopathy. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Sjogren-Larsson Syndrome (SLS)
- How many people
- 20 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Apr 2013to 30 Sep 2023
- How long will I take part?
- 5 Years
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: The study population will come from cohorts of Sjögren-Larsson syndrome patients currently followed at STAIR sites, from the RDCRN contact registry, and from the pool of new patients who directly contact STAIR sites or are referred to STAIR centers by their physicians.
Who may be able to join
- The only eligibility criterion is that subjects have a genetically or biochemically confirmed diagnosis of Sjogren-Larsson syndrome.
Who cannot join
- The primary exclusion criteria are the patients' failure to consent or inability to travel to a STAIR site.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Nebraska Medical Center
Omaha, Nebraska, 68198-5456
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
About this study
Official title: Sjogren-Larsson Syndrome: A Longitudinal Study of Natural History, Clinical Variation and Evaluation of Biochemical Markers
Sjogren-Larsson syndrome (SLS) is a rare genetic disease in which patients typically exhibit ichthyosis (dry, scaly skin), intellectual disability, spasticity, seizures and a distinctive maculopathy. The purpose of this study is to define the clinical spectrum and natural history of Sjogren-Larsson syndrome, and identify biomarkers that correlate with disease phenotype while establishing a registry for future investigations of biochemical pathogenesis and therapy.
Read the detailed description
The study will consist of a clinical component and a scientific component consisting of laboratory investigations of potentially useful biochemical (lipid and protein) markers. Up to 50 SLS patients of all ages, gender and ethnic origins will be enrolled. A detailed clinical evaluation will be performed to determine the presence and extent of disease involving the skin, nervous system and eyes. Clinical testing will include brain magnetic resonance imaging (MRI) and spectroscopy (MRS), electroencephalography (EEG), neurocognitive tests, ophthalmologic examination with retinal photographs and optical coherence tomography (OCT), photographs of the skin and tests of cutaneous transepidermal water loss. Laboratory investigations will include lipid analyses (e.g. fatty alcohols, farnesol, fatty acids, ether glycerolipids, etc.) of blood, skin and urine; proteomic analysis of skin (stratum corneum); and measurements of leukocyte fatty alcohol and farnesol oxidation. A skin biopsy (optional) will be obtained for electron microscopy, measurement of lanthanum perfusion (transepidermal water loss), and/or establishing keratinocyte cultures. Correlations between clinical abnormalities and laboratory measurements will be tested to identify the most useful biomarkers for future diagnostic and therapeutic studies. To characterize the progression of phenotypic features over time, patients <6 years of age will be followed yearly and patients ≥6 years of age will be followed every 3 years. In addition, a SLS patient registry will be established as a resource for future investigations in SLS.
- Conditions
- Sjogren-Larsson Syndrome (SLS)
- Keywords
- ichthyosis, spasticity, spastic diplegia, intellectual disability
- Medical subject headings
- Sjogren-Larsson Syndrome, Ichthyosis, Muscle Spasticity, Cerebral Palsy, Intellectual Disability
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 |
|---|---|---|
| Sjogren-Larsson syndrome | There are no cohorts for this study. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Characterize the extent and progression of neurocutaneous disease in patients with Sjogren-Larsson syndrome (SLS).
Determine the spectrum of clinical disease severity and changes in severity of symptoms over time. Each organ system will be evaluated using validated clinical exams (for example, Modified Ashworth Spasticity Score for neurologic severity) or categorical tests (such as EEG normal or abnormal). The clinical data will be used to develop a quantitative SLS severity score whereby patients will be described (for example, overall severity 1 to 5 with score 1 being the mildest phenotype and score 5 being the most severe). These quantitative outcome measures will be followed over time to assess disease progression.
Measured: 2017 (up to 5 years)
Secondary outcomes (1)
Identify biomarkers that correlate with disease severity.
Blood, urine and skin biomarkers will be explored to identify tests that correlate with clinical severity of SLS. Multiple tests will be performed and outcome measures will be statistically compared to the clinical severity score to determine correlation coefficients, which will be used to establish new biomarkers for SLS.
Measured: 2017 (up to 5 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2013 (estimated)
- Study start1 Apr 2013
- Primary completion31 Aug 2023
- Study completion30 Sep 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Sjogren-Larsson Syndrome (SLS)Studies of the same condition, open and under way.
- More trials run by University of NebraskaThe 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 only
- Time perspective
- Prospective
- Enrolment
- 20 participants (actual)
- Target duration
- 5 Years
Sponsor and investigators
- Lead sponsor
- University of Nebraska
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- William B Rizzo, MD, Study chair, University of Nebraska
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01971957
- Sponsor's protocol ID
- 0560-12-FB
- Acronym
- SLS
- Status last verified
- Oct 2024
- First submitted
- 30 Apr 2013
- Last updated
- 8 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Rizzo WB. Sjogren-Larsson syndrome: molecular genetics and biochemical pathogenesis of fatty aldehyde dehydrogenase deficiency. Mol Genet Metab. 2007 Jan;90(1):1-9. doi: 10.1016/j.ymgme.2006.08.006. Epub 2006 Sep 22.
PubMed 16996289Lossos A, Khoury M, Rizzo WB, Gomori JM, Banin E, Zlotogorski A, Jaber S, Abramsky O, Argov Z, Rosenmann H. Phenotypic variability among adult siblings with Sjogren-Larsson syndrome. Arch Neurol. 2006 Feb;63(2):278-80. doi: 10.1001/archneur.63.2.278.
PubMed 16476818Rizzo WB, Craft DA, Somer T, Carney G, Trafrova J, Simon M. Abnormal fatty alcohol metabolism in cultured keratinocytes from patients with Sjogren-Larsson syndrome. J Lipid Res. 2008 Feb;49(2):410-9. doi: 10.1194/jlr.M700469-JLR200. Epub 2007 Oct 30.
PubMed 17971613Fuijkschot J, Theelen T, Seyger MM, van der Graaf M, de Groot IJ, Wevers RA, Wanders RJ, Waterham HR, Willemsen MA. Sjogren-Larsson syndrome in clinical practice. J Inherit Metab Dis. 2012 Nov;35(6):955-62. doi: 10.1007/s10545-012-9518-6. Epub 2012 Jul 26.
PubMed 22833178Rizzo WB. The role of fatty aldehyde dehydrogenase in epidermal structure and function. Dermatoendocrinol. 2011 Apr;3(2):91-9. doi: 10.4161/derm.3.2.14619. Epub 2011 Apr 1.
PubMed 21695018Rizzo WB, Carney G. Sjogren-Larsson syndrome: diversity of mutations and polymorphisms in the fatty aldehyde dehydrogenase gene (ALDH3A2). Hum Mutat. 2005 Jul;26(1):1-10. doi: 10.1002/humu.20181.
PubMed 15931689Willemsen MA, Van Der Graaf M, Van Der Knaap MS, Heerschap A, Van Domburg PH, Gabreels FJ, Rotteveel JJ. MR imaging and proton MR spectroscopic studies in Sjogren-Larsson syndrome: characterization of the leukoencephalopathy. AJNR Am J Neuroradiol. 2004 Apr;25(4):649-57.
PubMed 15090362
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sjogren-Larsson Syndrome: A Longitudinal Study of Natural History, Clinical Variation and Evaluation of Biochemical Markers
- ClinicalTrials.gov ID
- NCT01971957
- Acronym / sponsor ID
- SLS / 0560-12-FB
- Conditions
- Sjogren-Larsson Syndrome (SLS)
- Keywords
- ichthyosis, spasticity, spastic diplegia, intellectual disability
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of NebraskaUniversity, hospital or other
- Study start
- 1 Apr 2013 (actual)
- Primary completion
- 31 Aug 2023 (actual)
- Study completion
- 30 Sep 2023 (actual)
- First posted
- 30 Oct 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.
Sjogren-Larsson syndrome (SLS) is a rare genetic disease in which patients typically exhibit ichthyosis (dry, scaly skin), intellectual disability, spasticity, seizures and a distinctive maculopathy. The purpose of this study is to define the clinical spectrum and natural history of Sjogren-Larsson syndrome, and identify biomarkers that correlate with disease phenotype while establishing a registry for future investigations of biochemical pathogenesis and therapy.
Detailed description
The study will consist of a clinical component and a scientific component consisting of laboratory investigations of potentially useful biochemical (lipid and protein) markers. Up to 50 SLS patients of all ages, gender and ethnic origins will be enrolled. A detailed clinical evaluation will be performed to determine the presence and extent of disease involving the skin, nervous system and eyes. Clinical testing will include brain magnetic resonance imaging (MRI) and spectroscopy (MRS), electroencephalography (EEG), neurocognitive tests, ophthalmologic examination with retinal photographs and optical coherence tomography (OCT), photographs of the skin and tests of cutaneous transepidermal water loss. Laboratory investigations will include lipid analyses (e.g. fatty alcohols, farnesol, fatty acids, ether glycerolipids, etc.) of blood, skin and urine; proteomic analysis of skin (stratum corneum); and measurements of leukocyte fatty alcohol and farnesol oxidation. A skin biopsy (optional) will be obtained for electron microscopy, measurement of lanthanum perfusion (transepidermal water loss), and/or establishing keratinocyte cultures. Correlations between clinical abnormalities and laboratory measurements will be tested to identify the most useful biomarkers for future diagnostic and therapeutic studies. To characterize the progression of phenotypic features over time, patients <6 years of age will be followed yearly and patients ≥6 years of age will be followed every 3 years. In addition, a SLS patient registry will be established as a resource for future investigations in SLS.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Target follow-up
- 5 Years
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sjogren-Larsson syndrome | – | –There are no cohorts for this study. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- The study population will come from cohorts of Sjögren-Larsson syndrome patients currently followed at STAIR sites, from the RDCRN contact registry, and from the pool of new patients who directly contact STAIR sites or are referred to STAIR centers by their physicians.
Key inclusion criteria (1 listed)
- The only eligibility criterion is that subjects have a genetically or biochemically confirmed diagnosis of Sjogren-Larsson syndrome.
Key exclusion criteria (1 listed)
- The primary exclusion criteria are the patients' failure to consent or inability to travel to a STAIR site.
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
Characterize the extent and progression of neurocutaneous disease in patients with Sjogren-Larsson syndrome (SLS).
Time frame: 2017 (up to 5 years)
Determine the spectrum of clinical disease severity and changes in severity of symptoms over time. Each organ system will be evaluated using validated clinical exams (for example, Modified Ashworth Spasticity Score for neurologic severity) or categorical tests (such as EEG normal or abnormal). The clinical data will be used to develop a quantitative SLS severity score whereby patients will be described (for example, overall severity 1 to 5 with score 1 being the mildest phenotype and score 5 being the most severe). These quantitative outcome measures will be followed over time to assess disease progression.
1 secondary outcome
Identify biomarkers that correlate with disease severity.
Time frame: 2017 (up to 5 years)
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 8 Oct 2024.
- Background: PubMed 16996289Rizzo WB. Sjogren-Larsson syndrome: molecular genetics and biochemical pathogenesis of fatty aldehyde dehydrogenase deficiency. Mol Genet Metab. 2007 Jan;90(1):1-9. doi: 10.1016/j.ymgme.2006.08.006. Epub 2006 Sep 22.
- Background: PubMed 16476818Lossos A, Khoury M, Rizzo WB, Gomori JM, Banin E, Zlotogorski A, Jaber S, Abramsky O, Argov Z, Rosenmann H. Phenotypic variability among adult siblings with Sjogren-Larsson syndrome. Arch Neurol. 2006 Feb;63(2):278-80. doi: 10.1001/archneur.63.2.278.
- Background: PubMed 17971613Rizzo WB, Craft DA, Somer T, Carney G, Trafrova J, Simon M. Abnormal fatty alcohol metabolism in cultured keratinocytes from patients with Sjogren-Larsson syndrome. J Lipid Res. 2008 Feb;49(2):410-9. doi: 10.1194/jlr.M700469-JLR200. Epub 2007 Oct 30.
- Background: PubMed 22833178Fuijkschot J, Theelen T, Seyger MM, van der Graaf M, de Groot IJ, Wevers RA, Wanders RJ, Waterham HR, Willemsen MA. Sjogren-Larsson syndrome in clinical practice. J Inherit Metab Dis. 2012 Nov;35(6):955-62. doi: 10.1007/s10545-012-9518-6. Epub 2012 Jul 26.
- Background: PubMed 21695018Rizzo WB. The role of fatty aldehyde dehydrogenase in epidermal structure and function. Dermatoendocrinol. 2011 Apr;3(2):91-9. doi: 10.4161/derm.3.2.14619. Epub 2011 Apr 1.
- Background: PubMed 15931689Rizzo WB, Carney G. Sjogren-Larsson syndrome: diversity of mutations and polymorphisms in the fatty aldehyde dehydrogenase gene (ALDH3A2). Hum Mutat. 2005 Jul;26(1):1-10. doi: 10.1002/humu.20181.
- Background: PubMed 15090362Willemsen MA, Van Der Graaf M, Van Der Knaap MS, Heerschap A, Van Domburg PH, Gabreels FJ, Rotteveel JJ. MR imaging and proton MR spectroscopic studies in Sjogren-Larsson syndrome: characterization of the leukoencephalopathy. AJNR Am J Neuroradiol. 2004 Apr;25(4):649-57.
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.
William B Rizzo, MD study chair
University of Nebraska
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Sjogren-Larsson Syndrome (SLS), run by University of Nebraska at 2 sites 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: finished, as of the sponsor's last update on 8 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
Characterize the extent and progression of neurocutaneous disease in patients with Sjogren-Larsson syndrome (SLS). (time frame: 2017 (up to 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 NCT01971957, which also lists 7 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 8 Oct 2024.