Glucose Metabolism in Sickle Cell Disease

• ClinicalTrials.gov Identifier: NCT02922296
• Recruitment Status: Recruiting
• First Posted: October 4, 2016
• Last Update Posted: June 13, 2023
• Sponsor: University of Illinois at Chicago
• Information provided by (Responsible Party): Victor Gordeuk, University of Illinois at Chicago

Tracking Information

• First Submitted Date: July 31, 2016
• First Posted Date: October 4, 2016
• Last Update Posted Date: June 13, 2023
• Study Start Date: May 1, 2015
• Estimated Primary Completion Date: May 1, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 29, 2016)

Metabolic status of adult SCD subjects [ Time Frame: through study completion, approximately one year after subject participation ]

The investigator will use the ATP III guidelines for definition of metabolic syndrome. A combination of any three of the following criteria will lead to the designation of metabolic syndrome:

• waist circumference >102 cm (men) or >88 cm (women)
• triglycerides ≥150 mg/dL
• HDL cholesterol <40 mg/dL (men) or <50 mg/dL (women)
• blood pressure ≥130/≥85 mg/dL (or recorded diagnosis of hypertension and use of antihypertensives)
• fasting glucose ≥110 mg/dL (or diagnosis of diabetes and use of anti-diabetic medications)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 29, 2016)

Genetic and genomic predictors in SCD subjects [ Time Frame: through study completion, approximately one year after subject participation ]

This will be accomplished by DNA linkage analysis and/or mutation analysis. In addition RNA will be isolated from from PBMCs and fractions of platelets, granulocytes and reticulocytes. The investigators will analyze the expression of transcripts to determine if alterations can explain the clinical observations.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Glucose Metabolism in Sickle Cell Disease
• Official Title: Glucose Metabolism in Sickle Cell Disease

Brief Summary

The purpose of the study is to better understand how the body handles sugars glucose and fats, such as cholesterol and triglycerides in sickle cell disease, and what puts certain persons at risk to develop diabetes. This understanding may help us to find new treatments to control blood sugar and prevent diabetes in people with and without sickle cell disease (SCD).

In this research, DNA and RNA will be isolated from blood cells. DNA will be used to find genes that cause or protect from diabetes, high cholesterol and high triglyceride, and RNA will be used for studies designed to find out how genes are doing their job of eventually producing proteins.

Detailed Description

Sickle cell disease (SCD) is due to homozygosity for a Glu6Val mutation in HBB (sickle cell anemia; hemoglobin SS) or to compound heterozygous forms like hemoglobin SC disease and hemoglobin S-β thalassemia. Past studies suggested a low prevalence of diabetes in patients with SCD.10 Improvements in treatment and care have increased the life span of patients. This, along with the wide availability of high calorie diets and increasing adiposity in SCD raises that possibility that the prevalence of diabetes is increasing in SCD. Our study is designed to characterize the changes in metabolism that occur in sickle cell disease and to identify clinical, genetic and genomic risk factors for the development of diabetes. Our hypothesis is that non-overweight subjects with SCD have relative protection from diabetes and metabolic syndrome, but that those individuals who do become overweight have a dramatic increase in the rates of diabetes and metabolic syndrome. Lean SCD subjects will not have simply a neutral, but an overtly anti-diabetic phenotype (e.g. better glucose tolerance and lower metabolic syndrome markers). The two main study aims are as follows; Aim 1. Define the metabolic status of adult SCD subjects according to normal or increased BMI.

Aim 2. Determine genetic and genomic predictors of overweight, metabolic syndrome and diabetes in SCD subjects.

• Study Type: Observational
• Study Design: Observational Model: Other; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

Blood samples will be stored temporarily in the laboratory of the Principal Investigator at the University of Illinois at Chicago, long term storage of specimens will be at the UIC Biobank. The research data will be stored in a locked file cabinet in the PI's research office. The patient's name or other identifying data will not be revealed, except to those directly involved in this study.

• Sampling Method: Non-Probability Sample
• Study Population: Adult sickle cell disease subjects, with or without diabetes.

Condition

• Sickle Cell Disease
• Diabetes Mellitus

• Intervention: Not Provided
• Study Groups/Cohorts: Not Provided
• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 29, 2016): 75
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 1, 2025
• Estimated Primary Completion Date: May 1, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Major sickling genotype (hemoglobin SS, Sbeta0-thalassemia, SOarab, SDpunjab)
• Age >35 years
• BMI <25 kg/m2 or >26 kg/m2
• Steady state, defined as >two weeks from a hospitalization for vaso-occlusive crisis, infection or surgery and not requiring immediate parenteral medication for pain control
• Fasting state (>8 hours since ingesting food or medication for diabetes)

Exclusion Criteria:

• Patients receiving insulin therapy
• Acute inflammatory or infectious illness or injury

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Victor Gordeuk, MD; 312-996-5680; vgordeuk@uic.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02922296
• Other Study ID Numbers: 2015-0366
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Victor Gordeuk, University of Illinois at Chicago
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Illinois at Chicago
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Victor Gordeuk, MD; University of Illinois at Chicago

• PRS Account: University of Illinois at Chicago
• Verification Date: June 2023