Gene-by-Stress Interactions in Intervention Studies Significance

The purpose of this study is to identify gene variants that increase risk of cardiovascular disease (CVD) and type 2 diabetes, particularly genes related to stress factors.

Study Overview

• Status: Terminated
• Conditions: Cardiovascular Diseases
• Intervention / Treatment: Drug: Ziprasidone; Drug: Lorcaserin; Drug: Placebo Oral Tablet

Detailed Description

In Aim 3, 100 subjects who participated in previous studies will be recruited to test the ability of a 5HTR2C agonist (lorcaserin) to increase and antagonist (ziprasidone) to reduce cortisol response to mental and metabolic stress in men carrying the rs6318 C allele and women in the rs6318 CC genotype of 5HTR2C. Lorcaserin is serotonin receptor agonist indicated for use as a weight loss drug. Ziprasidone is an antipsychotic indicated for treatment of bipolar disorder. Subjects will be treated with a single dose of each drug, 1 to 2 weeks apart, followed by a mental stress test and an oral glucose tolerance test with multiple blood draws. Each subject will also receive a placebo drug during one of the study visits.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and women who have been enrolled in the STRRIDE, ENHANCED, and/or REMIT studies age 18 years or greater.
• Ability and willingness to provide informed consent.
• Individuals with specific genotypes as determined from our previous work on their samples through Aim 1 of this project.

Exclusion Criteria:

• Women who are known to be pregnant, intend to become pregnant, or breast-feeding will be excluded. Women who are of child bearing potential (under age 55) will be informed that they will need to have their urine tested for pregnancy and that they should not participate in the research if they are not willing to have the Investigators provide them with information on positive pregnancy test results. Subjects will be informed that the pregnancy testing is not being performed for clinical purposes and that the testing is not a substitute for their regular medical care if they need to know whether or not they may be pregnant.
• History of Type II diabetes mellitus.
• History of prolonged QT interval.
• Participation in an investigational drug trial within the last 30 days.
• Already taking either ziprasidone or lorcaserin or any potential confounding medications, for example, other weight loss medications or psychotropic medications.
• Unwillingness to fast for at least 6 hours prior to the research study visit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ziprasidone; Ziprasidone 60 mg tablet by mouth, once a day for one day.	Drug: Ziprasidone; Given by mouth, single dose of 60 mg.; Other Names: Geodon
Active Comparator: Lorcaserin; Lorcaserin 20 mg tablet by mouth, once a day for one day.	Drug: Lorcaserin; Given by mouth, single dose of 20 mg.; Other Names: Belviq
Placebo Comparator: Placebo Oral Tablet; Sugar pill (in place of ziprasidone and lorcaserin) by mouth, once a day for one day.	Drug: Placebo Oral Tablet; Given by mouth, single dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in peak blood cortisol during the metabolic stress of an OGTT	Baseline to 3-hours post OGTT
Change in peak blood cortisol during the metabolic stress of a mental stress test	Baseline to 3-hours post mental stress test

Secondary Outcome Measures

Outcome Measure	Time Frame
Area-Under-the-Curve Glucose	Baseline to 2-hours post OGTT
Matsuda Insulin Resistance Index	Baseline to 2-hours post OGTT

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: William E Kraus, MD, Duke University

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2018
• Primary Completion (Actual): January 28, 2020
• Study Completion (Actual): January 28, 2020

Study Registration Dates

• First Submitted: January 4, 2017
• First Submitted That Met QC Criteria: January 4, 2017
• First Posted (Estimate): January 5, 2017

Study Record Updates

• Last Update Posted (Actual): February 17, 2020
• Last Update Submitted That Met QC Criteria: February 13, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Dopamine Agents; Serotonin Antagonists; Dopamine Antagonists; Ziprasidone
• Other Study ID Numbers: Pro00070047; 2P01HL036587-25 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No