NCT04275479

Diabetes/ Endocrine Surveillance in SDS

Endocrine Diabetes Screening in Patients With Shwachman-Diamond Syndrome DIABETES/ ENDOCRINE SURVEILLANCE IN SDS

• Status: Terminated
• Phase: —
• Study type: Observational
• Enrollment: 11 (actual)
• Sponsor: Washington University School of Medicine · Academic / Other
• Sex: All
• Age: 3 Years
• Healthy volunteers: Accepted

Summary

Shwachman-Diamond syndrome(SDS) is a rare autosomal recessive disorder involving primarily the Shwachman-Bodian-Diamond syndrome gene located on chromosome 7q11. The gene effects function of the 60S ribosome by interfering with the function of the Guanasine triphosphatase elongation factor 1 in the release of eukaryotic initiation factor 6 from the 60 S ribosomal subunit for translation initiation. Seventy five percent of the individual affected by the syndrome have a biallelic mutation (258+2T\>C and 183-184T \> CT). The syndrome results in defects primarily in the pancreas and bone marrow resulting in pancreatic insufficiency, leukopenia with an increased risk of infection and an increased risk for acute myelocytic leukemia. Animal models that have knocked out the function of the SBDS gene in the pancreas reveals at the pancreas at birth as well as the insulin producing cells in the pancreas are normal but subsequently developed fatty infiltration and apoptosis without inflammation resulting in pancreatic exocrine insufficiency with initially normal endocrine pancreatic function. The endocrine pancreatic function declines over time such that by 12 months of age these mice show a phenotype of impaired glucose tolerance. The finding of early onset diabetes is not yet considered a manifestation of this genetic defect but likely is occurring. This study is designed to assist in understanding the prevalence of glucose abnormalities in this syndrome. Exocrine pancreatic insufficiency leading to diabetes is a common hallmark of cystic fibrosis and cystic fibrosis related diabetes. Prevalence of glucose abnormalities in diabetes is a approaching 50% by the 2nd and 3rd decade of life in this disorder. The cystic fibrosis Foundation recommend screening for diabetes utilizing an oral glucose tolerance by the age of 10. Early diagnosis of diabetes in the syndrome as resulted in improved outcomes for patients with cystic fibrosis. It is my expectation that the prevalence of diabetes will be similar in SBDS patients. A small study performed I had the University of Cincinnati showed glucose abnormalities to occur in 5/20 individuals with the classic mutation. Investigators propose to screen patients with the classic mutation for diabetes and endocrine disease utilizing continuous glucose monitoring over a 14 day period in addition to baseline fasting blood tests for insulin, GAD 65 antibody, Fructosamine, A1c and C peptide.

Detailed description

The purpose of the study is to learn about how common early onset diabetes and other endocrine issues occur in people who have been diagnosed with SDS. Study procedures include: For participants with SDS: obtaining informed consent/assent; obtaining medical \& medication history, including history of diabetes, review of medical records and lab results for confirmation of diagnosis and inclusion/exclusion assessment; performance of a standard oral glucose tolerance test (OGTT) to be performed at a center close to the participants home, a modified oral glucose tolerance test and a modified mixed meal tolerance test to be performed by participant at home with phone access to study staff for directions, blood draws performed at a local lab or local physician office or other medical center in close proximity to the participants home. Completion of on-line, or in the case of no computer access - paper, questionnaires completed by the participant/parent to collect medical and health history, parents/siblings will be asked to complete a health history, 3 day food diary completed by participant/parent; phone calls; wearing of blinded continuous glucose monitoring device for 14 days; medical records release, 3-day diet diary; Additional optional biological specimens to look at cell free DNA and future biomarkers of endoplasmic reticulum stress in the beta cells of the pancreas will be obtained and stored for future study Parent(s) and/or siblings if willing and consented, will complete on-line medical history questionnaire and provide medical record release. Data to be obtained from on-going study for subjects with Cystic Fibrosis

Conditions

• Shwachman-Diamond Syndrome

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	Oral Glucose Tolerance Test	This is a two step process. Subjects will be asked to fast overnight,(no food and only water to drink for at least 8 hours). Then when subjects arrive for the visit,participants will have blood drawn and be asked to drink a sugary liquid. One hour later, another blood sample will be drawn and after two hours a final blood sample will be drawn.
OTHER	Modified Oral Glucose Tolerance Test	The participant will be asked to fast overnight (no food and only water to drink for at least 8 hours). There will be no blood drawn during this test, participant will be asked to drink a sugary liquid and to remaining fasting (water only) for the two hour after finishing the drink.
OTHER	Modified Mixed Meal Tolerance Test	The participant will be asked to fast overnight (no food and only water to drink for at least 8 hours). The participant will be given a meal supplement to drink in place of breakfast, for example Boost Plus. The participant will be asked to drink the meal supplement and to remaining fasting (water only) for the next two hours.
DEVICE	Continuous Glucose Monitor	The participant will be provided a CGM device to wear for 10 days during the study period. The CGM will be blinded (meaning that the participant will not be able to see the results).
OTHER	Food Diary	The participant will be asked to maintain a detailed food diary for 3 days during the 10 day study period.
OTHER	Medical History Questionnaires	The participant will be asked to provide detailed medical history

Timeline

• Start date: 2020-01-10
• Primary completion: 2022-12-30
• Completion: 2022-12-30
• First posted: 2020-02-19
• Last updated: 2024-08-19

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated device study