Effect of Nicotine on Brain Reward Pathways
Primary Purpose
Depressive Disorder
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Nicotine polacrilex
Sponsored by
About this trial
This is an interventional basic science trial for Depressive Disorder focused on measuring Nicotine, Depression
Eligibility Criteria
Inclusion Criteria for subjects with Major Depressive Disorder:
- Provide written informed consent;
- Both genders and all ethnic origins, age between 18 and 45;
- Meet DSM-IV diagnostic criteria for MDD (diagnosed with the use of the SCID);
- A baseline HAM-D score of 16 or greater;
- Absence of pregnancy;
Absence of any psychotropic medication for at least 2 weeks:
- 6 weeks for fluoxetine
- 6 months for neuroleptics
- 2 weeks for benzodiazepines
- 2 weeks for any other antidepressants
Inclusion Criteria for Healthy Controls
- Absence of medical, neurological, and psychiatric illness (including alcohol and substance abuse); as assessed by subject history and a structured clinical interview (SCID);
- Provide written informed consent;
- Both genders and all ethnic origins, age between 18 and 45;
- Absence of any medications for at least 3 weeks;
- Absence of pregnancy.
Exclusion Criteria:
- Subjects with suicidal ideation where outpatient treatment is determined unsafe. These patients will be immediately referred to a licensed psychologist or psychiatrist to determine the appropriate clinical treatment;
- Serious or unstable medical illness
- Lifetime history of seizure disorder;
- Lifetime history or current diagnosis of any of the following DSM-IV psychiatric illnesses: organic mental disorder, schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorders not otherwise specified, bipolar disorder, ADHD, patients with mood congruent or mood incongruent psychotic features; simple phobia, social anxiety disorder and generalized anxiety disorders will be allowed only if secondary to MDD;
- Patients with a lifetime history of electroconvulsive therapy (ECT);
- Failure to meet standard MRI safety requirements;
- May not have used any nicotine product in the past year; must report fewer than 20 lifetime uses of nicotine
- Must have an expired carbon monoxide level of less than or equal to 10 ppm.
- Use of anticholinergic drugs in the past week
- Any past or present history of cardiac problems including known arrhythmias, acute coronary syndrome, or ischemic heart disease
- Uncontrolled hypertension
- History of substance abuse in the past 6 months (other than caffeine), self-reported use of marijuana in past month, or history of treatment with methadone
- Heavy caffeine users (consume greater than 500 mg on a regular or daily basis)
- Subjects that cannot speak English
Sites / Locations
- McLean Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Nicotine
Placebo
Arm Description
2mg of nicotine in the form of a nicotine polacrilex lozenge will be administered orally, one time. 4mg of nicotine in the form of a nicotine polacrilex lozenge will be administered orally, one time.
Placebo comparator
Outcomes
Primary Outcome Measures
Change from Placebo in functional magnetic resonance imaging (fMRI) BOLD Response
Nicotine will enhance the fMRI BOLD response to monetary reinforcers relative to placebo administration
Secondary Outcome Measures
Full Information
NCT ID
NCT02346539
First Posted
January 14, 2015
Last Updated
March 21, 2018
Sponsor
Mclean Hospital
Collaborators
National Institute on Drug Abuse (NIDA)
1. Study Identification
Unique Protocol Identification Number
NCT02346539
Brief Title
Effect of Nicotine on Brain Reward Pathways
Official Title
Effect of Nicotine on Brain Reward Pathways
Study Type
Interventional
2. Study Status
Record Verification Date
March 2018
Overall Recruitment Status
Completed
Study Start Date
February 2015 (undefined)
Primary Completion Date
November 2017 (Actual)
Study Completion Date
November 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mclean Hospital
Collaborators
National Institute on Drug Abuse (NIDA)
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The investigators will determine whether an acute dose of nicotine, in the form of the nicotine lozenge, impacts brain and behavioral measures of mood and reward responsiveness in individuals with major depressive disorder.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Depressive Disorder
Keywords
Nicotine, Depression
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
46 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Nicotine
Arm Type
Experimental
Arm Description
2mg of nicotine in the form of a nicotine polacrilex lozenge will be administered orally, one time.
4mg of nicotine in the form of a nicotine polacrilex lozenge will be administered orally, one time.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo comparator
Intervention Type
Drug
Intervention Name(s)
Nicotine polacrilex
Other Intervention Name(s)
Nicotine lozenge
Intervention Description
Single Acute dose
Primary Outcome Measure Information:
Title
Change from Placebo in functional magnetic resonance imaging (fMRI) BOLD Response
Description
Nicotine will enhance the fMRI BOLD response to monetary reinforcers relative to placebo administration
Time Frame
Participants will be assessed during 2 fMRI scanning sessions, an expected average of 2 weeks.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria for subjects with Major Depressive Disorder:
Provide written informed consent;
Both genders and all ethnic origins, age between 18 and 45;
Meet DSM-IV diagnostic criteria for MDD (diagnosed with the use of the SCID);
A baseline HAM-D score of 16 or greater;
Absence of pregnancy;
Absence of any psychotropic medication for at least 2 weeks:
6 weeks for fluoxetine
6 months for neuroleptics
2 weeks for benzodiazepines
2 weeks for any other antidepressants
Inclusion Criteria for Healthy Controls
Absence of medical, neurological, and psychiatric illness (including alcohol and substance abuse); as assessed by subject history and a structured clinical interview (SCID);
Provide written informed consent;
Both genders and all ethnic origins, age between 18 and 45;
Absence of any medications for at least 3 weeks;
Absence of pregnancy.
Exclusion Criteria:
Subjects with suicidal ideation where outpatient treatment is determined unsafe. These patients will be immediately referred to a licensed psychologist or psychiatrist to determine the appropriate clinical treatment;
Serious or unstable medical illness
Lifetime history of seizure disorder;
Lifetime history or current diagnosis of any of the following DSM-IV psychiatric illnesses: organic mental disorder, schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorders not otherwise specified, bipolar disorder, ADHD, patients with mood congruent or mood incongruent psychotic features; simple phobia, social anxiety disorder and generalized anxiety disorders will be allowed only if secondary to MDD;
Patients with a lifetime history of electroconvulsive therapy (ECT);
Failure to meet standard MRI safety requirements;
May not have used any nicotine product in the past year; must report fewer than 20 lifetime uses of nicotine
Must have an expired carbon monoxide level of less than or equal to 10 ppm.
Use of anticholinergic drugs in the past week
Any past or present history of cardiac problems including known arrhythmias, acute coronary syndrome, or ischemic heart disease
Uncontrolled hypertension
History of substance abuse in the past 6 months (other than caffeine), self-reported use of marijuana in past month, or history of treatment with methadone
Heavy caffeine users (consume greater than 500 mg on a regular or daily basis)
Subjects that cannot speak English
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amy Janes, Ph.D
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
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
34198131
Citation
Wang KS, Brown K, Frederick BB, Moran LV, Olson D, Pizzagalli DA, Kaiser RH, Janes AC. Nicotine acutely alters temporal properties of resting brain states. Drug Alcohol Depend. 2021 Sep 1;226:108846. doi: 10.1016/j.drugalcdep.2021.108846. Epub 2021 Jun 24.
Results Reference
derived
Learn more about this trial
Effect of Nicotine on Brain Reward Pathways
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