Sjogren-Larsson Syndrome: Natural History, Clinical Variation and Evaluation of Biochemical Markers (SLS)

Tracking Information
First Submitted Date	April 30, 2013
First Posted Date	October 30, 2013
Last Update Posted Date	February 7, 2018
Study Start Date	April 2013
Estimated Primary Completion Date	July 2019 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures; (submitted: February 5, 2018)	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.
Original Primary Outcome Measures; (submitted: October 29, 2013)	Characterize the extent and progression of neurocutaneous disease in patients with Sjogren-Larsson syndrome, and identify useful biomarkers. [ Time Frame: 2017 (up to 5 years) ]
Change History	Complete list of historical versions of study NCT01971957 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures; (submitted: February 5, 2018)	Identify biomarkers that correlate with disease severity. [ Time Frame: 2017 (up to 5 years) ]; 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.
Original Secondary Outcome Measures	Not Provided
Current Other Outcome Measures	Not Provided
Original Other Outcome Measures	Not Provided
Descriptive Information
Brief Title	Sjogren-Larsson Syndrome: Natural History, Clinical Variation and Evaluation of Biochemical Markers
Official Title	Sjogren-Larsson Syndrome: A Longitudinal Study of Natural History, Clinical Variation and Evaluation of Biochemical Markers
Brief 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. 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 Type	Observational [Patient Registry]
Study Design	Observational Model: Case-Only; Time Perspective: Prospective
Target Follow-Up Duration	5 Years
Biospecimen	Retention: Samples Without DNA; Description: Blood, urine, skin
Sampling Method	Non-Probability Sample
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.
Condition	Sjogren-Larsson Syndrome (SLS)
Intervention	Not Provided
Study Groups/Cohorts	Sjogren-Larsson syndrome; There are no cohorts for this study.
Publications *	Rizzo WB. Sjögren-Larsson syndrome: molecular genetics and biochemical pathogenesis of fatty aldehyde dehydrogenase deficiency. Mol Genet Metab. 2007 Jan;90(1):1-9. Epub 2006 Sep 22. Review.; Lossos 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 Sjögren-Larsson syndrome. Arch Neurol. 2006 Feb;63(2):278-80.; Rizzo WB, Craft DA, Somer T, Carney G, Trafrova J, Simon M. Abnormal fatty alcohol metabolism in cultured keratinocytes from patients with Sjögren-Larsson syndrome. J Lipid Res. 2008 Feb;49(2):410-9. Epub 2007 Oct 30.; Fuijkschot J, Theelen T, Seyger MM, van der Graaf M, de Groot IJ, Wevers RA, Wanders RJ, Waterham HR, Willemsen MA. Sjögren-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. Review.; Rizzo 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.; Rizzo WB, Carney G. Sjögren-Larsson syndrome: diversity of mutations and polymorphisms in the fatty aldehyde dehydrogenase gene (ALDH3A2). Hum Mutat. 2005 Jul;26(1):1-10. Review.; Willemsen MA, Van Der Graaf M, Van Der Knaap MS, Heerschap A, Van Domburg PH, Gabreëls FJ, Rotteveel JJ. MR imaging and proton MR spectroscopic studies in Sjögren-Larsson syndrome: characterization of the leukoencephalopathy. AJNR Am J Neuroradiol. 2004 Apr;25(4):649-57.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status	Recruiting
Estimated Enrollment; (submitted: October 29, 2013)	50
Original Estimated Enrollment	Same as current
Estimated Study Completion Date	July 2019
Estimated Primary Completion Date	July 2019 (Final data collection date for primary outcome measure)
Eligibility Criteria	Inclusion Criteria: The only eligibility criterion is that subjects have a genetically or biochemically confirmed diagnosis of Sjogren-Larsson syndrome. Exclusion Criteria: The primary exclusion criteria are the patients' failure to consent or inability to travel to a STAIR site.
Sex/Gender	Sexes Eligible for Study: All
Ages	Child, Adult, Older Adult
Accepts Healthy Volunteers	No
Contacts	Contact: William B Rizzo, MD 402-559-2560 wrizzo@unmc.edu Contact: Sara M Jones, RD, LMNT 402-559-1747 saram.jones@unmc.edu
Listed Location Countries	United States
Removed Location Countries
Administrative Information
NCT Number	NCT01971957
Other Study ID Numbers	560-12
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	William Rizzo, MD, University of Nebraska
Study Sponsor	University of Nebraska
Collaborators	Not Provided
Investigators	Study Chair: William B Rizzo, MD University of Nebraska
PRS Account	University of Nebraska
Verification Date	February 2018