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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
Sponsored by
Mclean Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

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

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

First Posted
June 16, 2019
Last Updated
August 30, 2021
Sponsor
Mclean Hospital
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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
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

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
No
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
Email
ajanes@mclean.harvard.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Nathan Krantz, BA
Phone
(617) 855-2429‬
Email
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
Email
ajanes@mclean.harvard.edu

12. IPD Sharing Statement

Plan to Share IPD
No
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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