Progesterone and Brain Imaging Study

Phase 4

Completed

Conditions: Nicotine Withdrawal
Nicotine Dependence

Interventions: Drug: Progesterone
Drug: Placebo

Registration Number: NCT01954966

Lead Sponsor: University of Pennsylvania

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 81

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).

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Progesterone 200 mg capsules	Progesterone	Subjects will be prescribed progesterone 200 mg capsules by the study Principal Investigator. Subjects will take 200 mg of progesterone daily for four days.
Progesterone 200 mg look-alike capsules	Placebo	Subjects will be prescribed progesterone 200 mg look-alike placebo capsules by the study Principal Investigator. Subjects will take look-alike placebo capsules daily for four days.

Primary Outcome Measures

Name	Time	Method
GABA Pre and Post Progesterone Administration (Dorsolateral Pre-Frontal Cortex [DLPFC])	Test Day #2 and Test Day #5 - 6 total scans over the period of 2-3 months.	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.
GABA Pre and Post Progesterone Administration (Dorsal Anterior Cingulate Cortex [DACC])	Test Day #2 and Test Day #5 - 6 total scans over the period of 2-3 months.	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.

Secondary Outcome Measures

Name	Time	Method
Brief Questionnaire on Smoking Urges (BQSU)	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)	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.
Tiffany Questionnaire on Smoking Urges (TQSU)	Day 1 (pre smoking session, day 3 (PM), day 4 (PM), day 5 (pre smoking session)	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.
Profile of Mood States (POMS) Subscale: Anger-Hostility	Day 2 (pre and post scan), Day 5 (pre smoking session)	Profile of Mood States (POMS) Subscale: Anger-Hostility. This scale ranges from 0 to 48 with higher levels indicating higher levels of anger/hostility.
Visual Analog Scale (VAS) Question: Headache	Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)	Visual Analog Scale (VAS) question: Headache. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.
Visual Analog Scale (VAS) Question: Nauseous	Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)	Visual Analog Scale (VAS) question: Nauseous. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.
Profile of Mood States (POMS) Subscale: Tension-Anxiety	Day 2 (pre and post scan), Day 5 (pre smoking session)	Profile of Mood States (POMS) Subscale: Tension-Anxiety. This subscale ranges from 0-28 with higher levels indicating greater tension/anxiety.
Profile of Mood States (POMS) Subscale: Depression-Dejection	Day 2 (pre and post scan), Day 5 (pre smoking session)	Profile of Mood States (POMS) Subscale: Depression-Dejection. This subscale ranges from 0-60 with higher levels indicating greater depression/dejection.
Visual Analog Scale (VAS) Question: Hunger	Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)	Visual Analog Scale (VAS) question: Hunger. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.
Visual Analog Scale (VAS) Question: Sad	Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)	Visual Analog Scale (VAS) question: Sad. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.
Positive and Negative Affect Schedule (PANAS) Negative Affect	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)	Positive and Negative Affect Schedule (PANAS) Negative Affect Score. Ranges from 10-50 with higher scores representing higher levels of negative affect.
Nicotine Effects Questionnaire (NEQ) Question: Feels Good Effects of Nicotine	Day 1 (pre smoking session), Day 5 (post smoking session)	NEQ question: feels good effects of nicotine. Score ranges from 0 to 100 with higher levels indicating feeling more good effects of nicotine after smoking.
Nicotine Effects Questionnaire (NEQ) Question: Feels Bad Effects of Nicotine	Day 1 (pre smoking session), Day 5 (post smoking session)	Nicotine Effects Questionnaire (NEQ) question: feels bad effects of nicotine. Score ranges from 0 to 100 with higher levels indicating feeling more bad effects of nicotine after smoking.
Symptoms During Nicotine Abstinence (NWSC)	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)	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).
Profile of Mood States (POMS) Subscale: Fatigue	Day 2 (pre and post scan), Day 5 (pre smoking session)	Profile of Mood States (POMS) Subscale: Fatigue. This subscale ranges from 0 to 28 with higher scores indicating higher levels of fatigue.
Profile of Mood States (POMS) Subscale: Confusion-Bewilderment	Day 2 (pre and post scan), Day 5 (pre smoking session)	Profile of Mood States (POMS) Subscale: Confusion-Bewilderment. Ranges from 0 to 28 with higher levels indicating higher levels of confusion/bewilderment.
Visual Analog Scale (VAS) Question: Heartburn.	Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)	Visual Analog Scale (VAS) question: Heartburn. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.
Visual Analog Scale (VAS) Question: Anxious	Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)	Visual Analog Scale (VAS) question: Anxious. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.
Visual Analog Scale (VAS) Question: Tired	Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)	Visual Analog Scale (VAS) question: Tired. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.
Visual Analog Scale (VAS) Question: Irritable	Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)	Visual Analog Scale (VAS) question: Irritable. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.
Visual Analog Scale (VAS) Question: Happy	Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)	Visual Analog Scale (VAS) question: Happy. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.
Nicotine Effects Questionnaire (NEQ) Question: Feels Strength of Nicotine	Day 1 (pre smoking session), Day 5 (post smoking session)	Nicotine Effects Questionnaire (NEQ) question: feels strength of nicotine. Score ranges from 0 to 100 with higher levels indicating feeling stronger effects of nicotine after smoking.
Nicotine Effects Questionnaire (NEQ) Question: Head Rush	Day 1 (pre smoking session), Day 5 (post smoking session)	Nicotine Effects Questionnaire (NEQ) question: feels head rush. Score ranges from 0 to 100 with higher levels indicating feeling stronger/more intense head rush after smoking.
Visual Analog Scale (VAS) Question: Nervous	Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)	Visual Analog Scale (VAS) question: Nervous. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.
Profile of Mood State (POMS) Subscale: Vigor	Day 2 (pre and post scan), Day 5 (pre smoking session)	Profile of Mood State (POMS) Subscale: Vigor. Subscale ranges from 0 to 32, with higher levels indicating higher levels of vigor.
Visual Analog Scale (VAS) Question: Energetic	Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)	Visual Analog Scale (VAS) question: Energetic. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.
Visual Analog Scale (VAS) Question: Relaxed	Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)	Visual Analog Scale (VAS) question: Relaxed. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.
Visual Analog Scale (VAS) Question: Talkative	Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)	Visual Analog Scale (VAS) question: Headache. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.
Visual Analog Scale (VAS) Question: Calm	Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)	Visual Analog Scale (VAS) question: Calm. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.
Visual Analog Scale (VAS) Question: Depressed	Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)	Visual Analog Scale (VAS) question: Depressed. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.
Visual Analog Scale (VAS) Question: Drowsy	Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)	Visual Analog Scale (VAS) question: Drowsy. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.
Positive and Negative Affect Schedule (PANAS) Positive Affect	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)	Positive and Negative Affect Schedule (PANAS) Positive Affect Score. Ranges from 10-50 with higher scores representing higher levels of positive affect.