Thymalin
Thymulin, Thymic Factor, Serum Thymic Factor, Facteur Thymique Serique
Recruiting
OBSERVATIONAL
NCT06669949
Natural History of Sphingosine Phosphate Lyase Insufficiency Syndrome (SPLIS)
View on ClinicalTrials.gov
Updated Dec 15, 2025
Brief Summary
This is a prospective longitudinal natural history study with a retrospective cross-sectional arm aimed at determining the natural history of sphingosine phosphate lyase insufficiency syndrome (SPLIS), a recently recognized inborn error of metabolism. The central hypothesis is that age of onset, other disease features, and disease biomarkers will be predictive of quality of life (QOL) and survival in SPLIS patients.
Detailed Description
The main purpose of the study is to characterize the natural history of sphingosine phosphate lyase insufficiency syndrome (SPLIS) including the full spectrum of presentations (clinical, biochemical, radiological and pathological) and their change (progression or improvement) over time by collecting and analyzing data from prospective assessments on patients with SPLIS over a three-year time period and retrospective chart review of treatment history. By necessity, the investigators will also endeavor to explore the range of medical treatments and interventions currently being used in the care of SPLIS patients and their impact on the natural history of SPLIS. A retrospective arm will collect data on patients who are deceased and/or who are willing to share medical data but unwilling to participate in the prospective arm of the study. The secondary objective of the study is to establish a set of biomarkers including plasma sphingosine-1-phosphate (S1P) and absolute lymphocyte count (ALC) that may aid in: * Characterizing distinct phenotypic subgroups of SPLIS patients within the larger SPLIS population * Predicting the change (progression or improvement) in symptoms of SPLIS patients over time The exploratory objectives of the study are to explore the potential of plasma sphingolipids other than S1P, urinary sphingolipids including S1P, and immunological markers including cytokines and T cell subsets to serve as disease biomarkers. A SPLIS multi-domain responder index (MDRI) will be developed. Induced pluripotent stem cells derived from peripheral blood mononuclear cells and/or skin fibroblasts will be generated as a research tool.
Interventions
Name:
no intervention
Type:
OTHER
Description:
No interventions are involved in this observational study.
Primary Outcomes
Measure:
Survival
TimeFrame:
3 years
Description:
The primary outcome of this study is survival (age at death).
Measure:
Height
TimeFrame:
3 years
Description:
Standing height, sitting height and knee height in centimeters will be performed by stadiometer over time.
Measure:
Weight
TimeFrame:
3 years
Description:
Weight in kilograms will be measured by weight scale over time.
Measure:
Head circumference
TimeFrame:
3 years
Description:
Head circumference in centimeters will be measured by insertion tape over time.
Measure:
Triceps skin fold measurement
TimeFrame:
3 years
Description:
Skin fold in centimeters by skinfold calipers will be measured at the mid-triceps region over time.
Measure:
Subscapular skin fold measurement
TimeFrame:
3 years
Description:
Skin fold in centimeters by skinfold calipers will be measured at the subscapular region over time.
Measure:
Upper arm muscle circumference
TimeFrame:
3 years
Description:
Upper arm muscle circumference in centimeters will be measured using a tape measure over time.
Measure:
Sitting height
TimeFrame:
3 years
Description:
Sitting height in centimeters will be measured using a stadiometer over time.
Measure:
Knee height
TimeFrame:
3 years
Description:
Knee height in centimeters will be measured using a knee height caliper over time.
Measure:
Tibial length
TimeFrame:
3 years
Description:
Tibial length in centimeters will be measured using a tape measure over time.
Measure:
Nutritional intake assessment
TimeFrame:
3 years
Description:
A questionnaire assessing 24-hour recall of nutritional intake will be performed using using a 3-day food log. The information will be assessed using the online Automated Self-Administered 24-Hour Dietary Recall (ASA24) tool. The nutritional intake assessment will additionally include information on emesis and stool consistently using the Bristol Stool Chart.
Measure:
Retinal condition
TimeFrame:
3 years
Description:
Retinal condition will be assessed using a non-dilated eye exam.
Measure:
Skin condition
TimeFrame:
3 years
Description:
Appearance of acanthoses, ichthyosis, skin barrier function will be performed by a Tewameter instrument over time.
Measure:
Charcot Marie Tooth Neuropathy Score (CMTNS)
TimeFrame:
3 years
Description:
Charcot Marie Tooth neuropathy scores are made up of nine assessments, including three symptoms, four signs, and two neurophysiology items tested by nerve conduction study. Each assessment is scored on a scale of 0-4, with higher scores indicating greater impairment.
Measure:
Abdominal ultrasound
TimeFrame:
At baseline
Description:
An abdominal ultrasound will be performed to evaluate kidney and adrenal gland structure.
Measure:
Audiology testing
TimeFrame:
3 years
Description:
Hearing will be tested over time using standard audiology testing methods.
Measure:
Cognitive function
TimeFrame:
3 years
Description:
Cognitive function will be tested using the Vineland Adaptive Behavior Scales developmental test. The Vineland scales consist of questions about communication, daily living, socialization, and motor skills, and questions are targeted to age and developmental stage, rated on a scale of 0 (not able to perform behavior) to 2 (completely able to perform behavior). Cognitive testing will additionally include the Leiter-3.0, a nonverbal intelligence test designed to assess the cognitive abilities of individuals, primarily those who may have language or communication barriers. The exact interpretation of these scores is typically done by a trained psychologist or clinician, who will consider the test results in context with other information to provide a comprehensive assessment.
Measure:
Tanner stage
TimeFrame:
3 years
Description:
Sexual maturity will be determined by Tanner stage during physical exam. As Tanner stages move 1 through 5 to characterize the development of secondary sexual characteristics for males and females.
Measure:
Proteinuria
TimeFrame:
3 years
Description:
Proteinuria will be measured as urine albumin/creatinine ratio (ACR) determined with a 24 hour urine collection.
Measure:
Serum creatinine
TimeFrame:
3 years
Description:
Serum creatinine will be measured in mg/dL and used to determine estimated glomerular filtration rate (eGFR) in units of (mL/min/1.73m2) over time.
Measure:
Thyroid function
TimeFrame:
3 years
Description:
Free thyroxine (T4) and thyroid stimulating hormone by blood sample will be measured over time.
Measure:
Cortisol
TimeFrame:
3 years
Description:
Morning cortisol level in micrograms/deciliter by blood sample will be measured over time.
Measure:
Adrenocorticotropin hormone (ACTH)
TimeFrame:
3 years
Description:
ACTH in picograms per milliliter will be measured by blood sample over time.
Measure:
Renin
TimeFrame:
3 years
Description:
Blood renin measured in nanograms/milliliter/hour will be measured over time.
Measure:
Testosterone
TimeFrame:
3 years
Description:
Testosterone will be measured in nanograms/deciliter by blood sample over time.
Measure:
Estradiol
TimeFrame:
3 years
Description:
Estradiol will be measured in picograms per milliliter by blood sample over time.
Measure:
Anti-mullerian hormone (AMH)
TimeFrame:
3 years
Description:
Anti-mullerian hormone will be measured in nanograms/milliliter by blood sample over time.
Measure:
Inhibin B
TimeFrame:
3 years
Description:
Inhibin B will be measured in picograms per milliliter by blood sample over time.
Measure:
Follicle stimulating hormone (FSH)
TimeFrame:
3 years
Description:
Follicle stimulating hormone will be measured in milli international units per milliliter (mIU/ml) by blood sample over time.
Measure:
Luteinizing hormone (LH)
TimeFrame:
3 years
Description:
Luteinizing hormone will be measured in international units per liter (IU/L) by blood sample over time.
Measure:
Insulin-like growth factor 1 (IGF-1)
TimeFrame:
3 years
Description:
IGF-1 will be measured in nanograms/mL by blood over time.
Measure:
Blood glucose
TimeFrame:
3 years
Description:
Blood glucose will be measured in milligrams per deciliter by blood sample over time.
Measure:
Serum sodium
TimeFrame:
3 years
Description:
Serum sodium will be measured in milliequivalents per liter by blood sample over time.
Measure:
Serum potassium
TimeFrame:
3 years
Description:
Serum potassium will be measured in milliequivalents per liter by blood sample over time.
Measure:
Serum chloride
TimeFrame:
3 years
Description:
Serum chloride will be measured in milliequivalents per liter by blood sample over time.
Measure:
Serum carbon dioxide (CO2)
TimeFrame:
3 years
Description:
Serum CO2 will be measured in milliequivalents per liter by blood sample over time.
Measure:
Complete blood count
TimeFrame:
3 years
Description:
A complete automated blood count will be performed by blood sample over time.
Measure:
Serum immunoglobulins
TimeFrame:
3 years
Description:
Serum immunoglobulins (IgG, IgA, IgM) will be measured by blood sample over time.
Measure:
Antibodies to vaccine
TimeFrame:
At baseline
Description:
Antibodies to childhood vaccinations by blood sample will be measured.
Measure:
Blood urea nitrogen (BUN)
TimeFrame:
3 years
Description:
BUN will be measured in mg/dL by blood sample over time.
Measure:
Patient journey questionnaire
TimeFrame:
At baseline
Description:
A patient journey questionnaire capturing timing of disease feature onset and progression will be completed by the patient/family.
Measure:
Pediatric Quality of Life (PedsQL) Questionnaires
TimeFrame:
At baseline
Description:
PedsQL is a validated and standardized questionnaire capturing information on pediatric quality of life. The study will use 4 modules to capture various patients: End Stage Renal Disease Module, Family Impact Module, Generic Core Scales, and the Infant Scales. A higher score indicates a higher quality of life.
Measure:
Cholesterol panel
TimeFrame:
3 years
Description:
A cholesterol profile including high, low, and very low density lipoprotein (HDL, LDL, VLDL) and total cholesterol by blood sample will be measured.
Measure:
Pre- and Post-Kidney Transplant Questionnaire
TimeFrame:
3 years
Description:
A questionnaire capturing pre- and post-kidney transplant clinical information will be completed by the patient's physician (if applicable).
Measure:
Echocardiography
TimeFrame:
3 years
Description:
A standard cardiac ultrasound will be performed by a pediatric cardiologist to track SPLIS-related cardiovascular changes or abnormalities including left and chamber sizes and masses, Doppler measurements, and aortic diameter.
Measure:
Edema-Related Quality of Life
TimeFrame:
3 years
Description:
As SPLIS patients often experience edema as a result of kidney failure, PREPARE-NS is a questionnaire that will be used to gage how kidney failure symptoms like edema alter a patient's quality of living.
Measure:
Patient-Reported Outcomes Measurement Information System (PROMIS)
TimeFrame:
3 years
Description:
PROMIS assesses quality of life in several domains including physical functioning, mental health, social functioning, pain, sleep, fatigue, cognitive functioning, emotional distress, and ability to participate in social roles and activities. A higher score indicates a high quality of life.
Measure:
Cystatin C
TimeFrame:
3 years
Description:
Cystatin C will be measured in milligrams per liter (mg/L) or micrograms per milliliter (µg/mL) using a blood sample to assess kidney function.
Measure:
Urine specific gravity
TimeFrame:
3 years
Description:
Urine specific gravity will be measured using a urine sample, a unitless measure comparing the ratio of the density of urine to water, providing information about the kidney's ability to concentrate or dilute urine.
Measure:
Skin Barrier Function uingTewameter, Sebumeter, and Corneometer
TimeFrame:
3 years
Description:
Skin barrier function will be measured using a device called a Multi-Probe Adapter-5 (MPA5) manufactured by Courage + Khazaka, which uses a tewameter probe (measuring transepidermal water loss), a sebumeter (measuring skin sebum), and a corneometer (measuring skin hydration).
Trial Information
NCT ID
NCT06669949
Status
Recruiting
Study Type
OBSERVATIONAL
Sponsor
University of California, San Francisco
Last Updated
December 15, 2025