Progesterone and Brain Imaging Study

Phase 4CompletedNCT01954966

University of Pennsylvania81 enrolled

Overview

Male and female smokers were recruited to undergo 2 phases of smoking cessation. Each phase was 4 days long and involved 3 brain-imaging scans, blood draws and an intervention involving progesterone or a matched placebo.

The purpose of this study is to learn whether a sex hormone called progesterone is helpful in reducing cigarette smoking and craving for cigarettes. This study also includes brain imaging to measure possible effects of progesterone on certain neurochemicals. These neurochemicals are called gamma-aminobutyric acid (or GABA for short) and glutamate. Both nicotine and progesterone affect these brain chemicals. Individuals wishing to participate in this study must be medically healthy men or women who smoke at least 10 cigarettes per day or greater. Participants must not suffer from a mental illness or use drugs other than nicotine and marijuana. Participants cannot have any implanted metallic devices such as pacemakers, orthodontic braces, or shrapnel. Participants must not have peanut allergies and must never have had a reaction to progesterone. Finally, participants cannot be taking any medications for anxiety, depression or insomnia.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Nicotine Dependence Nicotine Withdrawal

Interventions

ProgesteroneDRUG

Participants will consume four pills of Progesterone over a period of four days. Participants will be asked to remain abstinent from smoking while taking Progesterone.

PlaceboDRUG

Participants will consume four pills of Placebo over a period of four days. Participants will be asked to remain abstinent from smoking while taking Placebo.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 50 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Female and male smokers, aged 18 to 50 years; * History of smoking greater than or equal to 10 cigarettes daily for the past year, as per self-report (periods of smoking abstinence within the last year will be exclusionary at PI discretion); * Not seeking treatment at the time of the study for nicotine dependence; * Have a Fagerstrom Test for Nicotine Dependence (FTND) score of at least 3 and a Carbon Monoxide (CO) level greater than or equal to 11 ppm; * Clean urine drug screen (marijuana is permissible); * In good health as verified by medical history; * For women, not pregnant as determined by pregnancy screening, nor breast feeding. Exclusion Criteria: * History of major medical illness: including liver diseases, abnormal vaginal bleeding, suspected or known malignancy; thrombophlebitis; deep vein thrombosis; pulmonary embolus; clotting or bleeding disorders; heart disease; diabetes; history of stroke or other medical conditions that the physician investigator deems as contraindicated for the patient to be in the study; * Regular use of psychotropic medication (antidepressants, antipsychotics, or anxiolytics) and recent (within previous year) psychiatric diagnosis and treatment for Axis I disorders including major depression, bipolar affective disorder, generalized anxiety disorder, post-traumatic stress disorder and panic disorder; * Lifetime history of schizophrenia or other psychotic disorder; * Lifetime substance dependence disorder, excepting nicotine, alcohol and marijuana, as per SCID interview * Substance use disorders within the previous 2 years, excepting nicotine, as per SCID interview * Regular use of any other tobacco products than cigarettes, including smokeless tobacco and nicotine products; * Known allergy to progesterone or peanuts (vehicle for micronized progesterone).

Locations (1)

Penn Center for Women's Behavioral Wellness

Philadelphia, Pennsylvania, United States

Outcomes

Primary Outcomes

GABA Pre and Post Progesterone Administration (Dorsal Anterior Cingulate Cortex [DACC])

GABA concentrations (collected in the Dorsal Anterior Cingulate Cortex \[DACC\]) will be obtained using the non-invasive neuroimaging method of proton magnetic resonance spectroscopy (1H-MRS) both before and after placebo administration and smoking abstinence. In total subjects will undergo 6 1H-MRS scans. The 6 1H-MRS scans take place over a period of approximately 1-2 months. Each paradigm (placebo/progesterone) takes approximately one week, with an approximately two-week wash in between paradigms for men and an approximately 1-month wash in between paradigms for women. The subject will undergo a smoking session on Test Day #1 and Test Day #5, MRS scans are conducted on Test Day #2 (2 scans) and Test Day #5 (1 scan). Minimal data is available for the primary outcome due to substantial issues with the 7T scanner. All subsequent scans were conducted on a 3T scanner which does not have the capacity to collect data on GABA.

Time frame: Test Day #2 and Test Day #5 - 6 total scans over the period of 2-3 months.

GABA Pre and Post Progesterone Administration (Dorsolateral Pre-Frontal Cortex [DLPFC])

GABA concentrations (collected in the Dorsolateral Pre-Frontal Cortex \[DLPFC\]) will be obtained using the non-invasive neuroimaging method of proton magnetic resonance spectroscopy (1H-MRS) both before and after placebo administration and smoking abstinence. In total subjects will undergo 6 1H-MRS scans. The 6 1H-MRS scans take place over a period of approximately 1-2 months. Each paradigm (placebo/progesterone) takes approximately one week, with an approximately two-week wash in between paradigms for men and an approximately 1-month wash in between paradigms for women. The subject will undergo a smoking session on Test Day #1 and Test Day #5, MRS scans are conducted on Test Day #2 (2 scans) and Test Day #5 (1 scan). Minimal data is available for the primary outcome due to substantial issues with the 7T scanner. All subsequent scans were conducted on a 3T scanner which does not have the capacity to collect data on GABA.

Time frame: Test Day #2 and Test Day #5 - 6 total scans over the period of 2-3 months.

Secondary Outcomes

Symptoms During Nicotine Abstinence (NWSC)

Data from ClinicalTrials.gov

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Withdrawal symptoms will be measured using the Nicotine Withdrawal Symptoms Checklist (NWSC). The scale ranges from a minimum of 0 to a maximum of 28, with higher scores indicating greater withdrawal (more withdrawal symptoms, higher intensity/severity of withdrawal).

Time frame: Day 1 (pre and post smoking session, day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)

Brief Questionnaire on Smoking Urges (BQSU)

Craving will be assessed using the Brief Questionnaire on Smoking Urges (BQSU). It ranges from 7-70 with higher levels indicating higher levels of nicotine craving.

Time frame: Day 1 (pre and post smoking session, day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)

Tiffany Questionnaire on Smoking Urges (TQSU)

Craving will also be assessed using the Tiffany Questionnaire for Smoking Urges. It ranges from 32 to 224 with higher scores indicated higher levels of smoking urges/craving.

Time frame: Day 1 (pre smoking session, day 3 (PM), day 4 (PM), day 5 (pre smoking session)

Profile of Mood States (POMS) Subscale: Tension-Anxiety

Profile of Mood States (POMS) Subscale: Tension-Anxiety. This subscale ranges from 0-28 with higher levels indicating greater tension/anxiety.

Time frame: Day 2 (pre and post scan), Day 5 (pre smoking session)

Profile of Mood States (POMS) Subscale: Depression-Dejection

Profile of Mood States (POMS) Subscale: Depression-Dejection. This subscale ranges from 0-60 with higher levels indicating greater depression/dejection.

Time frame: Day 2 (pre and post scan), Day 5 (pre smoking session)

Profile of Mood States (POMS) Subscale: Anger-Hostility

Profile of Mood States (POMS) Subscale: Anger-Hostility. This scale ranges from 0 to 48 with higher levels indicating higher levels of anger/hostility.

Time frame: Day 2 (pre and post scan), Day 5 (pre smoking session)

Profile of Mood States (POMS) Subscale: Fatigue

Profile of Mood States (POMS) Subscale: Fatigue. This subscale ranges from 0 to 28 with higher scores indicating higher levels of fatigue.

Time frame: Day 2 (pre and post scan), Day 5 (pre smoking session)

Profile of Mood State (POMS) Subscale: Vigor

Profile of Mood State (POMS) Subscale: Vigor. Subscale ranges from 0 to 32, with higher levels indicating higher levels of vigor.

Time frame: Day 2 (pre and post scan), Day 5 (pre smoking session)

Profile of Mood States (POMS) Subscale: Confusion-Bewilderment

Profile of Mood States (POMS) Subscale: Confusion-Bewilderment. Ranges from 0 to 28 with higher levels indicating higher levels of confusion/bewilderment.

Time frame: Day 2 (pre and post scan), Day 5 (pre smoking session)

Visual Analog Scale (VAS) Question: Headache

Visual Analog Scale (VAS) question: Headache. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.