NCT04275479

Diabetes/ Endocrine Surveillance in SDS

Terminated Last updated 19 August 2024

What this trial tests

trial testing Oral Glucose Tolerance Test in Shwachman-Diamond Syndrome in 11 participants. Terminated before completion.

Timeline

10 January 2020

Primary endpoint
30 December 2022

30 December 2022

Quick facts

Lead sponsor	Washington University School of Medicine
Status	Terminated
Study type	OBSERVATIONAL
Enrollment	11
Start date	10 January 2020
Primary completion	30 December 2022
Estimated completion	30 December 2022
Sites	1 location across United States

Drugs / interventions tested

• Oral Glucose Tolerance Test — full drug profile →
• Modified Oral Glucose Tolerance Test
• Modified Mixed Meal Tolerance Test
• Continuous Glucose Monitor
• Food Diary
• Medical History Questionnaires

Conditions studied

• Shwachman-Diamond Syndrome — all drugs for Shwachman-Diamond Syndrome →

Sponsor

Washington University School of Medicine

Who can join

3 and older, any sex, with Shwachman-Diamond Syndrome. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial.