NCT06669949 · University of California, San Francisco
Natural History of Sphingosine Phosphate Lyase Insufficiency Syndrome (SPLIS)
(SPLIS-HIS)
What this study is about
This is a forward-looking longitudinal natural history study with a reviewing past data cross-sectional treatment group$1 aimed at determining the natural history of sphingosine phosphate lyase insufficiency syndrome (SPLIS), a recently recognized inborn error of metabolism.
View original scientific description
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.
Interventions
OTHER
no intervention
No interventions are involved in this observational study.
Primary outcome measures
Survival
Time frame: 3 years
The primary outcome of this study is survival (age at death).
Height
Time frame: 3 years
Standing height, sitting height and knee height in centimeters will be performed by stadiometer over time.
Weight
Time frame: 3 years
Weight in kilograms will be measured by weight scale over time.
Head circumference
Time frame: 3 years
Head circumference in centimeters will be measured by insertion tape over time.
Triceps skin fold measurement
Time frame: 3 years
Skin fold in centimeters by skinfold calipers will be measured at the mid-triceps region over time.
Subscapular skin fold measurement
Time frame: 3 years
Skin fold in centimeters by skinfold calipers will be measured at the subscapular region over time.
Upper arm muscle circumference
Time frame: 3 years
Upper arm muscle circumference in centimeters will be measured using a tape measure over time.
Sitting height
Time frame: 3 years
Sitting height in centimeters will be measured using a stadiometer over time.
Knee height
Time frame: 3 years
Knee height in centimeters will be measured using a knee height caliper over time.
Tibial length
Time frame: 3 years
Tibial length in centimeters will be measured using a tape measure over time.
Nutritional intake assessment
Time frame: 3 years
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.
Retinal condition
Time frame: 3 years
Retinal condition will be assessed using a non-dilated eye exam.
Skin condition
Time frame: 3 years
Appearance of acanthoses, ichthyosis, skin barrier function will be performed by a Tewameter instrument over time.
Charcot Marie Tooth Neuropathy Score (CMTNS)
Time frame: 3 years
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.
Abdominal ultrasound
Time frame: At baseline
An abdominal ultrasound will be performed to evaluate kidney and adrenal gland structure.
Audiology testing
Time frame: 3 years
Hearing will be tested over time using standard audiology testing methods.
Cognitive function
Time frame: 3 years
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.
Tanner stage
Time frame: 3 years
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.
Proteinuria
Time frame: 3 years
Proteinuria will be measured as urine albumin/creatinine ratio (ACR) determined with a 24 hour urine collection.
Serum creatinine
Time frame: 3 years
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.
Thyroid function
Time frame: 3 years
Free thyroxine (T4) and thyroid stimulating hormone by blood sample will be measured over time.
Cortisol
Time frame: 3 years
Morning cortisol level in micrograms/deciliter by blood sample will be measured over time.
Adrenocorticotropin hormone (ACTH)
Time frame: 3 years
ACTH in picograms per milliliter will be measured by blood sample over time.
Renin
Time frame: 3 years
Blood renin measured in nanograms/milliliter/hour will be measured over time.
Testosterone
Time frame: 3 years
Testosterone will be measured in nanograms/deciliter by blood sample over time.
Estradiol
Time frame: 3 years
Estradiol will be measured in picograms per milliliter by blood sample over time.
Anti-mullerian hormone (AMH)
Time frame: 3 years
Anti-mullerian hormone will be measured in nanograms/milliliter by blood sample over time.
Inhibin B
Time frame: 3 years
Inhibin B will be measured in picograms per milliliter by blood sample over time.
Follicle stimulating hormone (FSH)
Time frame: 3 years
Follicle stimulating hormone will be measured in milli international units per milliliter (mIU/ml) by blood sample over time.
Luteinizing hormone (LH)
Time frame: 3 years
Luteinizing hormone will be measured in international units per liter (IU/L) by blood sample over time.
Insulin-like growth factor 1 (IGF-1)
Time frame: 3 years
IGF-1 will be measured in nanograms/mL by blood over time.
Blood glucose
Time frame: 3 years
Blood glucose will be measured in milligrams per deciliter by blood sample over time.
Serum sodium
Time frame: 3 years
Serum sodium will be measured in milliequivalents per liter by blood sample over time.
Serum potassium
Time frame: 3 years
Serum potassium will be measured in milliequivalents per liter by blood sample over time.
Serum chloride
Time frame: 3 years
Serum chloride will be measured in milliequivalents per liter by blood sample over time.
Serum carbon dioxide (CO2)
Time frame: 3 years
Serum CO2 will be measured in milliequivalents per liter by blood sample over time.
Complete blood count
Time frame: 3 years
A complete automated blood count will be performed by blood sample over time.
Serum immunoglobulins
Time frame: 3 years
Serum immunoglobulins (IgG, IgA, IgM) will be measured by blood sample over time.
Antibodies to vaccine
Time frame: At baseline
Antibodies to childhood vaccinations by blood sample will be measured.
Blood urea nitrogen (BUN)
Time frame: 3 years
BUN will be measured in mg/dL by blood sample over time.
Patient journey questionnaire
Time frame: At baseline
A patient journey questionnaire capturing timing of disease feature onset and progression will be completed by the patient/family.
Pediatric Quality of Life (PedsQL) Questionnaires
Time frame: At baseline
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.
Cholesterol panel
Time frame: 3 years
A cholesterol profile including high, low, and very low density lipoprotein (HDL, LDL, VLDL) and total cholesterol by blood sample will be measured.
Pre- and Post-Kidney Transplant Questionnaire
Time frame: 3 years
A questionnaire capturing pre- and post-kidney transplant clinical information will be completed by the patient's physician (if applicable).
Echocardiography
Time frame: 3 years
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.
Edema-Related Quality of Life
Time frame: 3 years
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.
Patient-Reported Outcomes Measurement Information System (PROMIS)
Time frame: 3 years
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.
Cystatin C
Time frame: 3 years
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.
Urine specific gravity
Time frame: 3 years
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.
Skin Barrier Function uingTewameter, Sebumeter, and Corneometer
Time frame: 3 years
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).
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- Potential subjects fulfilling the following criteria will be eligible to participate in this study:
- Living or deceased patients diagnosed with SPLIS based on
- harbor biallelic pathogenic variant (PV) or likely PV (LPV) in the SGPL1 gene, regardless of phenotype OR
- harbor nucleotide changes in both SGPL1 alleles, regardless of variant classification, if they also have one of the following: b1) exhibit at least 1 phenotypic feature of SPLIS (nephrosis, endocrine defect, ichthyosis, neuropathy, male gonadal dysgenesis, lymphopenia) b2) have evidence from biochemical or molecular data (such as enzyme expression or activity in skin fibroblasts) that indicate a possible loss of function in the S1P lyase (SPL) protein b3) are a sibling of a subject with nucleotide changes in both alleles of SGPL1 and at least 1 phenotypic feature of SPLIS
- Informed consent and (if appropriate) assent for living subjects. For deceased subjects, the Principal Investigator (PI) will be responsible for ensuring that all requirements have been met in regard to the relevant local laws and regulations. Parents of participating SPLIS patients may be included as controls.
Exclusion criteria
- Subjects with SPLIS (or their parents) who are currently using or have a history of using an investigational agent in the last 30 days with the exception of off-label use of medications will be excluded from the study
Where
- San Francisco, California
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced May 13, 2025 · Source of record for eligibility and locations