Diabetes/ Endocrine Surveillance in SDS

NCT ID: NCT04275479

Last Updated: 2024-08-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Total Enrollment

11 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-01-10

Study Completion Date

2022-12-30

Brief Summary

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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

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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

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Shwachman-Diamond Syndrome

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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SDS - without Diabetes diagnosis

SDS - without Diabetes diagnosis

Oral Glucose Tolerance Test

Intervention Type DIAGNOSTIC_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.

Modified Oral Glucose Tolerance Test

Intervention Type OTHER

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.

Modified Mixed Meal Tolerance Test

Intervention Type OTHER

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.

Continuous Glucose Monitor

Intervention Type DEVICE

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).

Food Diary

Intervention Type OTHER

The participant will be asked to maintain a detailed food diary for 3 days during the 10 day study period.

Medical History Questionnaires

Intervention Type OTHER

The participant will be asked to provide detailed medical history

SDS with Diabetes Diagnosis

SDS with Diabetes Diagnosis

Modified Mixed Meal Tolerance Test

Intervention Type OTHER

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.

Continuous Glucose Monitor

Intervention Type DEVICE

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).

Food Diary

Intervention Type OTHER

The participant will be asked to maintain a detailed food diary for 3 days during the 10 day study period.

Medical History Questionnaires

Intervention Type OTHER

The participant will be asked to provide detailed medical history

Cystic Fibrosis (CF) patients data & lab results

De-identified data from age matched population norms, CF patients associated pancreatic insufficiency known or treated diabetes

No interventions assigned to this group

Interventions

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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.

Intervention Type DIAGNOSTIC_TEST

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.

Intervention Type 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.

Intervention Type OTHER

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).

Intervention Type DEVICE

Food Diary

The participant will be asked to maintain a detailed food diary for 3 days during the 10 day study period.

Intervention Type OTHER

Medical History Questionnaires

The participant will be asked to provide detailed medical history

Intervention Type OTHER

Other Intervention Names

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OGTT Modified OGTT MMTT CGM

Eligibility Criteria

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Inclusion Criteria

Population 1: SDS and non-diabetic

* Age: 3 years of age and older to allow for baseline blood to be drawn. The Cystic Fibrosis group has seen glucose abnormalities well before age 10 but recommends screening after age 10. Investigators are attempting to define the population and will screen starting at age 3 to get a baseline data set.
* Willing to provide consent/ assent
* Stable health in the last month- i.e. not hospitalized/ ill in the last 6 weeks
* Patients should have been on stable medications for at least 4 weeks prior to testing - This includes neupogen and other white cell stimulators.
* Classic SBDS mutation with pancreatic insufficiency as determined by medical history.
* Able/willing to have a standard OGTT and modified OGTT
* Able/ willing to wear a Libre- Pro sensor and have sensor returned. If not willing to wear CGM- willing to do a standard OGTT as described.
* Not currently on diabetic therapy or labeled as diabetic.
* Willing to complete a health survey in regard to the SBDS and endocrine History

Population 2: SDS and Labeled as diabetic

* Age greater than 3
* If labeled as diabetic - obtain data for age of onset and treatment utilized for the diabetes
* Willing to provide consent/ assent and complete health survey for SBDS and endocrine history
* Willing/able to wear 14 day blinded Libre-Pro to assess the response to current therapy and food diary.
* Willing to provide Fasting labs as outlined above for the group- no OGT, just the mixed meal tolerance test

Population 1 and 2 Future Sub-study: Assess alpha cell and insulin dynamic response

* Participant in primary study who agree to the sub-study
* Willing to travel to St. Louis for clamp procedure.
* Budget will determine the actual number to be screened.
* Travel will be included.

Population 3: Control groups

* Other control groups for the study will be age matched population norms, Cystic Fibrosis patients associated pancreatic insufficiency known or treated diabetes.
Minimum Eligible Age

3 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Shwachman Diamond Syndrome Foundation

UNKNOWN

Sponsor Role collaborator

Barnes-Jewish Hospital

OTHER

Sponsor Role collaborator

Washington University School of Medicine

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Garry Tobin, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

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Washington University

St Louis, Missouri, United States

Site Status

Countries

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United States

References

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Related Links

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https://shwachman-diamond.org/

Shwachman-Diamond Syndrome Foundation

https://sites.wustl.edu/wuvfh/

Washington University Research Participant Registry

https://wuphysicians.wustl.edu/clinical-trials/understanding-clinical-trials

Washington University- Understanding Clinical Trials

Other Identifiers

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201909102

Identifier Type: -

Identifier Source: org_study_id

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