Validation of a Novel Screening Test for Maternal Insulin Resistance

Insulin Resistance, Diabetes Clinical Trial

Official title:

Validation of a Novel Screening Test for Maternal Insulin Resistance and Predicting Maternal Fetal Outcomes: A Pilot Study.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03388697
• Other study ID #: 17-0228
• Status: Completed
• Start date: December 15, 2017
• Est. completion date: July 15, 2019

Study information

• Verified date: February 2019
• Source: The University of Texas Medical Branch, Galveston
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This will be a validation study of Quantose IR and Quantose IGT to predict insulin resistance and identify patients with prediabetes. This is a pilot study of 100 subjects. Based on the results of this initial trial, investigators plan to perform a larger trial at UTMB.

Quantose IR is a fasting blood test for insulin resistance and prediabetes, and is clinically validated in non-pregnant individuals. The Quantose IR Score is based on three novel nonglycemic biomarkers, as well as insulin, and provides a comprehensive measure of insulin resistance. These analytes include:

• α-HB (α-hydroxybutyrate): positively correlated with insulin resistance and indicative of early β-cell dysfunction.

• L-GPC (linoleoyl-glycerophosphocholine): negatively correlated with insulin resistance and impaired glucose tolerance.

• Oleic Acid: positively correlated with increasing lipolysis and insulin resistance.

• Insulin: increased insulin is characteristic of insulin resistance and is an independent risk factor for type 2 diabetes and cardiovascular disease.

Quantose IGT is designed to estimate the risk of being IGT. It is calculated from a multiple logistic regression model based on the fasting plasma levels of:

• Glucose.

• α−HB.

• β−HB.

• 4-methyl-2-oxopentanoic acid.

• LGPC.

• Oleic acid.

• Serine.

• Vitamin B5. Participants in the study will be consenting to data collection and two visits for lab draw. The investigators will then evaluate the performance of the Quantose IR and Quantose IGT in the study population.

Description:

This is a prospective cohort non-interventional study. Subjects will be identified during the time of a prenatal visit at one of the UTMB clinics. All necessary institutional and regulatory approval will be obtained prior to enrolling any candidates for this study.

Potential subjects that are not patients of the investigator or patients of the study team members, they will not be contacted by study staff unless they have been informed of the study by their medical provider and express an interest in receiving more information on the study or wish to enroll in the study. Under the direction of the PI, trained research staff will be available in the UTMB prenatal care clinics to screen and consent subjects according to study protocol. The Perinatal Research Division (PRD) has staff based in the UTMB Maternal Health (OB) clinics. These research staff members will screen the charts and electronic medical records of prenatal patients receiving care in the OB clinics. In order to contact potential study participants, the HIPAA waiver is submitted.

In addition, the OB clinic staff will be in serviced on the study and encouraged to refer potential subjects to the PRD staff. Other than the blood samples for this study, the management of pregnancy and delivery will be according to the standard of care at UTMB and will be up to the clinical provider.

Blood samples will be collected during 2 windows, early window (gestational age 10 0/7 to 13 6/7 weeks) and late window (gestational age 24 0/7 to 28 0/7 weeks) and stored at -800C in our perinatal research division. An aliquot will be sent to Metabolon to run the Quantose IR and Quantose IGT. The laboratory and the investigators will be blinded to the outcomes of the patient.

Testing using Quantose IR and Quantose IGT: The blood draws will be timed to coincide with clinically indicated blood tests as much as possible (e.g. first visit labs, aneuploidy screening, gestational diabetes screening).

Testing using HOMA IR: The investigators will be measuring fasting insulin and glucose levels (last meal more than 8hrs before testing i.e. overnight fasting) from EDTA-plasma samples. After collection, the samples will be spun and plasma obtained. Samples will be stored until testing.

Two tubes (total = 20cc) of blood will be collected from participants who will be asked to fast for minimum of 8 hours prior to blood draw.

The samples from both time points will be sent together to Metabolon for Quantose IR and Quantose IGT analysis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: July 15, 2019
• Est. primary completion date: July 15, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• 18 years or older.

• Singleton pregnancy.

• Able to provide consent.

• Gestational age 10 0/7 to 13 6/7 weeks.

• Planned delivery at UTMB (John Sealy Hospital (JSH) or League City Hospital Campus.

• Pre-pregnancy or early pregnancy BMI > or = 30 kg/m2

Exclusion Criteria:

-

Related Conditions & MeSH terms

• Insulin Resistance
• Insulin Resistance, Diabetes

Intervention

Diagnostic Test:
• Quantose IR and Quantose IGT analysis
Testing using Quantose IR and Quantose IGT: The blood draws will be timed to coincide with clinically indicated blood tests as much as possible (e.g. first visit labs, aneuploidy screening, gestational diabetes screening).
• HOMA IR the standard testing for insulin resistance
Testing using HOMA IR: Investigators will be measuring fasting insulin and glucose levels (last meal more than 8hrs before testing i.e. overnight fasting) from EDTA-plasma samples. After collection, the samples will be spun and plasma obtained. Samples will be stored until testing. The investigators will be using the following computation to calculate HOMA.

Locations

Country	Name	City	State
United States	Ashley Salazar	Galveston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
The University of Texas Medical Branch, Galveston

Country where clinical trial is conducted

United States, 

References & Publications (4)

Ginsberg H, Olefsky JM, Reaven GM. Further evidence that insulin resistance exists in patients with chemical diabetes. Diabetes. 1974 Aug;23(8):674-8. — View Citation

Harris MI. Epidemiologic studies on the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM). Clin Invest Med. 1995 Aug;18(4):231-9. Review. — View Citation

Lyssenko V, Jonsson A, Almgren P, Pulizzi N, Isomaa B, Tuomi T, Berglund G, Altshuler D, Nilsson P, Groop L. Clinical risk factors, DNA variants, and the development of type 2 diabetes. N Engl J Med. 2008 Nov 20;359(21):2220-32. doi: 10.1056/NEJMoa0801869. — View Citation

Reaven GM. Insulin resistance and human disease: a short history. J Basic Clin Physiol Pharmacol. 1998;9(2-4):387-406. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Gestational Diabetes	Development of gestational diabetes (based on the two step approach: 1hr glucose screen > 135mg/dL and 2/4 abnormal values in a 3 hr OGTT using the Carpenter and Coustan	Up to 28 0/7 weeks of gestation
Secondary	Insulin resistance	Defined as abnormal HOMA IR	Up to 28 0/7 weeks of gestation
Secondary	Fasting Plasma glucose	Measuring plasma glucose	Up to 28 0/7 weeks of gestation
Secondary	Fasting Insulin	Measuring plasma insulin level	Up to 28 0/7 weeks of gestation
Secondary	1 hour glucola	after receiving 50grams glucose load po and plasma glucose level is drawn 1 hour later	Up to 28 0/7 weeks of gestation
Secondary	Perinatal death	stillbirths plus early neonatal deaths (under 7 days)	up to 7 days after delivery
Secondary	Neonatal hypoglycemia	Neonate plasma glucose < 90mg/dL	up to 7 days after delivery
Secondary	NICU admission	Admission to the neonatal intensive care unit	up to 7 days after delivery