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Dexmedetomidine for Reversal of Cocaine's Effects on the Heart

Primary Purpose

Chest Pain, Acute Coronary Syndrome

Status

Completed

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

Dexmedetomidine

Normal Saline

Intranasal cocaine

About this trial

This is an interventional treatment trial for Chest Pain focused on measuring Cocaine, Dexmedetomidine, Myocardial Contrast Echocardiography

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Healthy adult subjects ages of 18-65 years without any history of substance abuse (other than tobacco), including narcotics, abuse of prescription painkillers, cocaine or any other recreational drug

Exclusion Criteria:

Known or suspected right-to-left, bi-directional, or transient right-to-left cardiac shunts or detected by screening echocardiogram performed prior to I.V. infusion of Definity microbubbles
Hypersensitivity or prior reactions to Definity microbubbles
Pregnant or nursing women
Any evidence of cardiopulmonary disease by history or physical examination, including subjects who are taking any cardiovascular medications of any sort
History of hypertension or BP at time of consent > 140/90 mm Hg
Any history of substance abuse (other than tobacco), including narcotics, prescription painkillers, cocaine or any other recreational drug (any person that says they have EVER tried these drugs will be excluded from this study)
Subjects reporting alcohol intake of more than 2 drinks/day
Severe psychiatric illness (e.g., schizophrenia, suicidal depression) in addition to drug dependence, which may signify a high risk of addiction
Diabetes mellitus or any other systemic illness
Individuals with a history of pseudocholinesterase deficiency
Hypersensitivity to dexmedetomidine or lorazepam
The presence of alcohol by breathalyzer
Subjects who have poor echocardiography images will be screen failed.
Persons with mechanically, magnetically, or electrically activated implants, such as cardiac pacemakers, neurostimulators, and infusion pumps (MRI only).
Persons with ferromagnetic implants and ferromagnetic foreign bodies, such as intracranial, aneurysm clips, shrapnel and intraocular metal chips as these could become dislodged (MRI only).
Persons unable to tolerate MRI imaging secondary to an inability to lie supine or severe claustrophobia (MRI only).
Persons whose renal function test does not meet CSMC standard of care MRI contrast protocol requirements (GFR <45ml/min).
Persons with allergy to animal dander or animal-instigated asthma
Persons with a history of kidney or liver disease.

Sites / Locations

Cedars-Sinai

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Dexmedetomidine and intranasal cocaine

Normal saline and intranasal cocaine

Arm Description

Intranasal cocaine administration (2 mg/kg) then Dexmedetomidine (0.3-0.6 mcg/kg) infusion

Intranasal cocaine administration (2 mg/kg) then Saline (over 10 minutes I.V. infusion)

Outcomes

Primary Outcome Measures

Myocardial Perfusion

Myocardial perfusion will be measured by myocardial contrast echocardiography after dexmedetomidine administration and compared to baseline. There will be no repeat dosing of dexmedetomidine. No longer term outcomes are measured.

Secondary Outcome Measures

Full Information

NCT ID

NCT01927640

First Posted

August 19, 2013

Last Updated

January 10, 2020

Sponsor

Cedars-Sinai Medical Center

Collaborators

Lincy Foundation

1. Study Identification

Unique Protocol Identification Number

NCT01927640

Brief Title

Dexmedetomidine for Reversal of Cocaine's Effects on the Heart

Official Title

Study of Dexmedetomidine for the Reversal of Cocaine's Effects on Myocardial Perfusion

Study Type

Interventional

2. Study Status

Record Verification Date

April 2018

Overall Recruitment Status

Completed

Study Start Date

February 1, 2013 (Actual)

Primary Completion Date

January 15, 2014 (Actual)

Study Completion Date

January 15, 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Cedars-Sinai Medical Center

Collaborators

Lincy Foundation

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

This study will use myocardial contrast echocardiography performed during a continuous intravenous infusion of Definity microbubbles (Perflutren lipid microbubbles) to determine if dexmedetomidine (an intravenous central sympatholytic drug) can reverse all the cardiovascular effects of low-dose intranasal cocaine-including vasoconstriction in the coronary microcirculation-both in cocaine-naïve and non-treatment seeking cocaine-addicted subjects.

Detailed Description

Each subject will be participating in three study visits: Screening Visit, Visit 1: a low-dose dobutamine visit and Visit 2: a low-dose cocaine visit. At the dobutamine visit, the subject will only receive low-dose dobutamine, which will be used as an internal inotropic/vasodilator control for cocaine. At the cocaine visit, the subject will receive low-dose intranasal cocaine followed by either the active study drug (dexmedetomidine) or an inactive placebo (saline). Both cocaine and dobutamine will increase myocardial contractility and oxygen demand, thereby stimulating metabolic vasodilation. If, as predicted, cocaine also causes α-adrenergic agonist in the coronary microcirculation, then myocardial blood flow should increase less with cocaine then with dobutamine for a given level of myocardial oxygen demand. We will study if dexmedetomidine, a central sympatholytic, can normalize this cocaine effect. We previously have used dobutamine as a comparator for cocaine in our research. At both visits, myocardial contrast echocardiography will be used to measure regional myocardial perfusion.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chest Pain, Acute Coronary Syndrome

Keywords

Cocaine, Dexmedetomidine, Myocardial Contrast Echocardiography

7. Study Design

Primary Purpose

Treatment

Study Phase

Early Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

115 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Dexmedetomidine and intranasal cocaine

Arm Type

Experimental

Arm Description

Intranasal cocaine administration (2 mg/kg) then Dexmedetomidine (0.3-0.6 mcg/kg) infusion

Arm Title

Normal saline and intranasal cocaine

Arm Type

Placebo Comparator

Arm Description

Intranasal cocaine administration (2 mg/kg) then Saline (over 10 minutes I.V. infusion)

Intervention Type

Drug

Intervention Name(s)

Dexmedetomidine

Other Intervention Name(s)

Precedex

Intervention Description

Dexmedetomidine (0.3-0.6 mcg/kg) infusion.

Intervention Type

Drug

Intervention Name(s)

Normal Saline

Intervention Description

Normal saline infusion (10 cc)

Intervention Type

Drug

Intervention Name(s)

Intranasal cocaine

Intervention Description

Intranasal cocaine (2 mg/kg)

Primary Outcome Measure Information:

Title

Myocardial Perfusion

Description

Time Frame

Baseline and Immediately after acute administration of study drug (Day 1)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Healthy adult subjects ages of 18-65 years without any history of substance abuse (other than tobacco), including narcotics, abuse of prescription painkillers, cocaine or any other recreational drug Exclusion Criteria: Known or suspected right-to-left, bi-directional, or transient right-to-left cardiac shunts or detected by screening echocardiogram performed prior to I.V. infusion of Definity microbubbles Hypersensitivity or prior reactions to Definity microbubbles Pregnant or nursing women Any evidence of cardiopulmonary disease by history or physical examination, including subjects who are taking any cardiovascular medications of any sort History of hypertension or BP at time of consent > 140/90 mm Hg Any history of substance abuse (other than tobacco), including narcotics, prescription painkillers, cocaine or any other recreational drug (any person that says they have EVER tried these drugs will be excluded from this study) Subjects reporting alcohol intake of more than 2 drinks/day Severe psychiatric illness (e.g., schizophrenia, suicidal depression) in addition to drug dependence, which may signify a high risk of addiction Diabetes mellitus or any other systemic illness Individuals with a history of pseudocholinesterase deficiency Hypersensitivity to dexmedetomidine or lorazepam The presence of alcohol by breathalyzer Subjects who have poor echocardiography images will be screen failed. Persons with mechanically, magnetically, or electrically activated implants, such as cardiac pacemakers, neurostimulators, and infusion pumps (MRI only). Persons with ferromagnetic implants and ferromagnetic foreign bodies, such as intracranial, aneurysm clips, shrapnel and intraocular metal chips as these could become dislodged (MRI only). Persons unable to tolerate MRI imaging secondary to an inability to lie supine or severe claustrophobia (MRI only). Persons whose renal function test does not meet CSMC standard of care MRI contrast protocol requirements (GFR <45ml/min). Persons with allergy to animal dander or animal-instigated asthma Persons with a history of kidney or liver disease.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ronald G Victor, MD

Organizational Affiliation

Cedars-Sinai Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Cedars-Sinai

City

Los Angeles

State/Province

California

ZIP/Postal Code

90048

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

23283356

Citation

Kontak AC, Victor RG, Vongpatanasin W. Dexmedetomidine as a novel countermeasure for cocaine-induced central sympathoexcitation in cocaine-addicted humans. Hypertension. 2013 Feb;61(2):388-94. doi: 10.1161/HYPERTENSIONAHA.112.203554. Epub 2013 Jan 2.

Results Reference

background

PubMed Identifier

17692748

Citation

Menon DV, Wang Z, Fadel PJ, Arbique D, Leonard D, Li JL, Victor RG, Vongpatanasin W. Central sympatholysis as a novel countermeasure for cocaine-induced sympathetic activation and vasoconstriction in humans. J Am Coll Cardiol. 2007 Aug 14;50(7):626-33. doi: 10.1016/j.jacc.2007.03.060. Epub 2007 Jul 30.

Results Reference

background

PubMed Identifier

11877354

Citation

Tuncel M, Wang Z, Arbique D, Fadel PJ, Victor RG, Vongpatanasin W. Mechanism of the blood pressure--raising effect of cocaine in humans. Circulation. 2002 Mar 5;105(9):1054-9. doi: 10.1161/hc0902.104714.

Results Reference

background

PubMed Identifier

12044126

Citation

Crandall CG, Vongpatanasin W, Victor RG. Mechanism of cocaine-induced hyperthermia in humans. Ann Intern Med. 2002 Jun 4;136(11):785-91. doi: 10.7326/0003-4819-136-11-200206040-00006.

Results Reference

background

PubMed Identifier

10430763

Citation

Vongpatanasin W, Mansour Y, Chavoshan B, Arbique D, Victor RG. Cocaine stimulates the human cardiovascular system via a central mechanism of action. Circulation. 1999 Aug 3;100(5):497-502. doi: 10.1161/01.cir.100.5.497.

Results Reference

background

PubMed Identifier

9045864

Citation

Jacobsen TN, Grayburn PA, Snyder RW 2nd, Hansen J, Chavoshan B, Landau C, Lange RA, Hillis LD, Victor RG. Effects of intranasal cocaine on sympathetic nerve discharge in humans. J Clin Invest. 1997 Feb 15;99(4):628-34. doi: 10.1172/JCI119205.

Results Reference

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Dexmedetomidine for Reversal of Cocaine's Effects on the Heart

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