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Targeting Orexin to Treat Nicotine Dependence

Primary Purpose

Nicotine Dependence

Status

Unknown status

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Suvorexant 20 mg

Suvorexant 10 mg

Placebo oral tablet

About this trial

This is an interventional basic science trial for Nicotine Dependence

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Participants will be male and female volunteers between the ages of 18-50
Participants must report daily smoking of at least 5 cigarettes per day over the last 6 months.
Participants must be nicotine dependent, having an FTND score greater than or equal to 4.
Participants must have an expired carbon monoxide level of 10 ppm or more on the screening day.
Participants must have an expired carbon monoxide level of no more than 10 ppm on the study visits.
Female participants must have a negative pregnancy test on all study days.

Exclusion Criteria:

Participants cannot meet DSM-5 criteria for lifetime and/or current psychotic disorders such as bipolar disorder, schizophrenia, schizoaffective disorder
Participants cannot meet DSM-5 criteria for current substance abuse disorders other than nicotine and marihuana and cannot meet criteria for current moderate or severe alcohol use disorder (as assessed by the SCID-5)
Participants cannot have positive drug and alcohol screen on each study visit other than for nicotine or marijuana.
Participants reporting marihuana use greater than 1-2 times per week will be excluded.
Participants must report no marihuana use within 24 hours of the study visit.
Participants cannot be taking any prescription medication that could impact brain function including medications that depress CNS function
Participants cannot have a history of major head trauma resulting in cognitive impairment, seizure, or other neurological disorders.
Participants cannot be pregnant or breastfeeding.
Participants must be able to read screening materials including consent form and give informed consent
Individuals with severe hepatic impairment will be excluded.
Participants cannot be obese as determined by a Body Mass Index (BMI) of 30 or greater.
Participants cannot be using a CYP3A inhibitor/inducer (metabolism by CYP3A is the major elimination pathway for suvorexant)
Participants cannot have a current cardiac disorder such as palpitations, tachycardia and/or use of the cardiac medication Digoxin
Participants cannot have narcolepsy
Participants cannot self-report complex sleep behaviors such as sleep driving, preparing and eating food or making phone calls
Participants cannot have compromised respiratory function such severe obstructive sleep apnea or severe chronic obstructive pulmonary disease
Participants cannot have current major depressive disorder (within the past 6 months) and/or indorse suicidal ideation on the Beck Depression Inventory.

Sites / Locations

McLean HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Suvorexant 10mg

Suvorexant 20mg

Arm Description

Suvorexant 10mg oral dose

Suvorexant 20mg oral dose

Outcomes

Primary Outcome Measures

Nicotine Craving

Total average value on the Questionnaire of Smoking Urges (QSU): and average values for Factors 1 and 2

Nicotine withdrawal

Wisconsin Smoking Withdrawal Scale: Total average value

Secondary Outcome Measures

Somnolence

Stanford Sleepiness Scale (SSS)

Full Information

NCT ID

NCT03999099

First Posted

June 16, 2019

Last Updated

August 30, 2021

Sponsor

Mclean Hospital

1. Study Identification

Unique Protocol Identification Number

NCT03999099

Brief Title

Targeting Orexin to Treat Nicotine Dependence

Official Title

Targeting Orexin to Treat Nicotine Dependence

Study Type

Interventional

2. Study Status

Record Verification Date

August 2021

Overall Recruitment Status

Unknown status

Study Start Date

September 26, 2019 (Actual)

Primary Completion Date

May 30, 2022 (Anticipated)

Study Completion Date

June 30, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Mclean Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

5. Study Description

Brief Summary

Tobacco smoking continues to be the primary cause of preventable mortality in the United States. Despite the availability of smoking cessation aids, the majority of those trying to quit smoking end up relapsing. Thus, there is a strong need to evaluate alternative treatment targets such as orexin antagonists, which have shown promise in preclinical models at reducing the motivational aspects of drug use.The current work will evaluate the influence of orexin antagonism on several factors impacting the motivation to smoke.

Detailed Description

Tobacco use leads to ~440,000 deaths and a loss of $193 billion every year in the US. This public health and economic crisis continues as no interventions effectively prevent smoking relapse. Between 40-70% of smokers are unable to maintain abstinence and 75% of those who do attain abstinence will relapse within one-year. These relapse rates remain high even when using currently available cessation aids, which primarily target the cholinergic system, suggesting the need for medications with novel targets such as orexin. The current proposal will improve scientific knowledge and/or clinical practice by translating preclinical research on orexin into the clinical domain by indicating: 1) whether orexin antagonism attenuates motivational factors associated with smoking relapse, 2) whether suvorexant shows promise as a smoking cessation aid, or 3) whether suvorexant contributes too many unwanted side effects despite mitigating the motivation to smoke, thus confirming the role of orexin in nicotine dependence and indicating the need to develop more specific orexin antagonists.

6. Conditions and Keywords

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

Nicotine Dependence

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Model Description

A single group will undergo three study visits where, on different days, they will receive placebo, 10 mg, or 20 mg lorcaserin.

Masking

ParticipantInvestigatorOutcomes Assessor

Masking Description

The order or medication/placebo administration will be randomized. The study staff and participant will be blinded to which medication they are receiving.

Allocation

Randomized

Enrollment

45 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Title

Suvorexant 10mg

Arm Type

Experimental

Arm Description

Suvorexant 10mg oral dose

Arm Title

Suvorexant 20mg

Arm Type

Experimental

Arm Description

Suvorexant 20mg oral dose

Intervention Type

Drug

Intervention Name(s)

Suvorexant 20 mg

Intervention Description

Suvorexant at a high dose (20 mg)

Intervention Type

Drug

Intervention Name(s)

Suvorexant 10 mg

Intervention Description

Suvorexant at a low dose (10 mg)

Intervention Type

Drug

Intervention Name(s)

Placebo oral tablet

Intervention Description

Placebo

Primary Outcome Measure Information:

Title

Nicotine Craving

Description

Total average value on the Questionnaire of Smoking Urges (QSU): and average values for Factors 1 and 2

Time Frame

approximately 4 hours post drug administration and following exposure to visual smoking cues

Title

Nicotine withdrawal

Description

Wisconsin Smoking Withdrawal Scale: Total average value

Time Frame

approximately 4 hours post drug administration

Secondary Outcome Measure Information:

Title

Somnolence

Description

Stanford Sleepiness Scale (SSS)

Time Frame

approximately 4 hours post drug administration

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Participants will be male and female volunteers between the ages of 18-50 Participants must report daily smoking of at least 5 cigarettes per day over the last 6 months. Participants must be nicotine dependent, having an FTND score greater than or equal to 4. Participants must have an expired carbon monoxide level of 10 ppm or more on the screening day. Participants must have an expired carbon monoxide level of no more than 10 ppm on the study visits. Female participants must have a negative pregnancy test on all study days. Exclusion Criteria: Participants cannot meet DSM-5 criteria for lifetime and/or current psychotic disorders such as bipolar disorder, schizophrenia, schizoaffective disorder Participants cannot meet DSM-5 criteria for current substance abuse disorders other than nicotine and marihuana and cannot meet criteria for current moderate or severe alcohol use disorder (as assessed by the SCID-5) Participants cannot have positive drug and alcohol screen on each study visit other than for nicotine or marijuana. Participants reporting marihuana use greater than 1-2 times per week will be excluded. Participants must report no marihuana use within 24 hours of the study visit. Participants cannot be taking any prescription medication that could impact brain function including medications that depress CNS function Participants cannot have a history of major head trauma resulting in cognitive impairment, seizure, or other neurological disorders. Participants cannot be pregnant or breastfeeding. Participants must be able to read screening materials including consent form and give informed consent Individuals with severe hepatic impairment will be excluded. Participants cannot be obese as determined by a Body Mass Index (BMI) of 30 or greater. Participants cannot be using a CYP3A inhibitor/inducer (metabolism by CYP3A is the major elimination pathway for suvorexant) Participants cannot have a current cardiac disorder such as palpitations, tachycardia and/or use of the cardiac medication Digoxin Participants cannot have narcolepsy Participants cannot self-report complex sleep behaviors such as sleep driving, preparing and eating food or making phone calls Participants cannot have compromised respiratory function such severe obstructive sleep apnea or severe chronic obstructive pulmonary disease Participants cannot have current major depressive disorder (within the past 6 months) and/or indorse suicidal ideation on the Beck Depression Inventory.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Amy Janes, PhD

Phone

(617)855-3244

ajanes@mclean.harvard.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Nathan Krantz, BA

Phone

(617) 855-2429‬

nkrantz@mclean.harvard.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Amy Janes, PhD

Organizational Affiliation

Mclean Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

McLean Hospital

City

Belmont

State/Province

Massachusetts

ZIP/Postal Code

02478

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Amy C Janes, PhD

Phone

617-855-3244

ajanes@mclean.harvard.edu

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

2343783

Citation

Brandon TH, Tiffany ST, Obremski KM, Baker TB. Postcessation cigarette use: the process of relapse. Addict Behav. 1990;15(2):105-14. doi: 10.1016/0306-4603(90)90013-n.

Results Reference

background

PubMed Identifier

19008791

Citation

Centers for Disease Control and Prevention (CDC). Smoking-attributable mortality, years of potential life lost, and productivity losses--United States, 2000-2004. MMWR Morb Mortal Wkly Rep. 2008 Nov 14;57(45):1226-8.

Results Reference

background

PubMed Identifier

19160228

Citation

Hajek P, Stead LF, West R, Jarvis M, Lancaster T. Relapse prevention interventions for smoking cessation. Cochrane Database Syst Rev. 2009 Jan 21;(1):CD003999. doi: 10.1002/14651858.CD003999.pub3.

Results Reference

background

PubMed Identifier

12365880

Citation

Hall SM, Humfleet GL, Reus VI, Munoz RF, Hartz DT, Maude-Griffin R. Psychological intervention and antidepressant treatment in smoking cessation. Arch Gen Psychiatry. 2002 Oct;59(10):930-6. doi: 10.1001/archpsyc.59.10.930.

Results Reference

background

PubMed Identifier

28498504

Citation

Rohsenow DJ, Tidey JW, Martin RA, Colby SM, Swift RM, Leggio L, Monti PM. Varenicline versus nicotine patch with brief advice for smokers with substance use disorders with or without depression: effects on smoking, substance use and depressive symptoms. Addiction. 2017 Oct;112(10):1808-1820. doi: 10.1111/add.13861. Epub 2017 Jul 4.

Results Reference

background

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Targeting Orexin to Treat Nicotine Dependence

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