Targeting Orexin to Treat Nicotine Dependence

NCT03999099 | Unknown Phase 1 FDA Drug

• 1 other identifier: Orexin and Nicotine
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

Nicotine Dependence

Outcome Measures

Primary Outcomes (2)

• Nicotine Craving

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

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

• Nicotine withdrawal

  Wisconsin Smoking Withdrawal Scale: Total average value

  approximately 4 hours post drug administration

Secondary Outcomes (1)

• Somnolence

  approximately 4 hours post drug administration

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Drug: Placebo oral tablet

Suvorexant 10mg

EXPERIMENTAL

Suvorexant 10mg oral dose

Drug: Suvorexant 10 mg

Suvorexant 20mg

EXPERIMENTAL

Suvorexant 20mg oral dose

Drug: Suvorexant 20 mg

Interventions

Suvorexant 20 mg DRUG

Suvorexant at a high dose (20 mg)

Suvorexant 20mg

Suvorexant 10 mg DRUG

Suvorexant at a low dose (10 mg)

Suvorexant 10mg

Placebo oral tablet DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Mclean Hospital: lead

Study Sites (1)

McLean Hospital

Belmont, Massachusetts, 02478, United States

RECRUITING

Related Publications (5)

• 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.

  PMID: 2343783 BACKGROUND

• 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.

  PMID: 19008791 BACKGROUND

• 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.

  PMID: 19160228 BACKGROUND

• 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.

  PMID: 12365880 BACKGROUND

• 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.

  PMID: 28498504 BACKGROUND

MeSH Terms

Conditions

Tobacco Use Disorder

Interventions

suvorexant

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Study Officials

• Amy Janes, PhD

  Mclean Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amy Janes, PhD

CONTACT

(617)855-3244; ajanes@mclean.harvard.edu

Nathan Krantz, BA

CONTACT

(617) 855-2429‬; nkrantz@mclean.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The order or medication/placebo administration will be randomized. The study staff and participant will be blinded to which medication they are receiving.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry, HMS and Director, McLean Imaging Center

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

Study Record Dates

• First Submitted: June 16, 2019
• First Posted: June 26, 2019
• Study Start: September 26, 2019
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: January 5, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)