Progesterone and Brain Imaging Study

Nicotine Dependence Clinical Trial

Official title:

Multimodal Imaging of Progesterone/Neurosteroid Effects in Nicotine Addiction

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01954966
• Other study ID #: 811940
• Secondary ID: K24DA030301
• Status: Completed
• Phase: Phase 4
• Start date: November 2010
• Est. completion date: December 2021

Study information

• Verified date: June 2022
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 81
• Est. completion date: December 2021
• Est. primary completion date: December 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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).

Related Conditions & MeSH terms

• Nicotine Dependence
• Nicotine Withdrawal
• Tobacco Use Disorder

Intervention

Drug:
• Progesterone
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.
• Placebo
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.

Locations

Country	Name	City	State
United States	Penn Center for Women's Behavioral Wellness	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
University of Pennsylvania	National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

United States, 

References & Publications (5)

Cai K, Nanga RP, Lamprou L, Schinstine C, Elliott M, Hariharan H, Reddy R, Epperson CN. The impact of gabapentin administration on brain GABA and glutamate concentrations: a 7T ¹H-MRS study. Neuropsychopharmacology. 2012 Dec;37(13):2764-71. doi: 10.1038/npp.2012.142. Epub 2012 Aug 8. — View Citation

Cosgrove KP, Mitsis EM, Bois F, Frohlich E, Tamagnan GD, Krantzler E, Perry E, Maciejewski PK, Epperson CN, Allen S, O'malley S, Mazure CM, Seibyl JP, van Dyck CH, Staley JK. 123I-5-IA-85380 SPECT imaging of nicotinic acetylcholine receptor availability in nonsmokers: effects of sex and menstrual phase. J Nucl Med. 2007 Oct;48(10):1633-40. Epub 2007 Sep 14. — View Citation

Epperson CN, O'Malley S, Czarkowski KA, Gueorguieva R, Jatlow P, Sanacora G, Rothman DL, Krystal JH, Mason GF. Sex, GABA, and nicotine: the impact of smoking on cortical GABA levels across the menstrual cycle as measured with proton magnetic resonance spectroscopy. Biol Psychiatry. 2005 Jan 1;57(1):44-8. — View Citation

Epperson CN, Toll B, Wu R, Amin Z, Czarkowski KA, Jatlow P, Mazure CM, O'Malley SS. Exploring the impact of gender and reproductive status on outcomes in a randomized clinical trial of naltrexone augmentation of nicotine patch. Drug Alcohol Depend. 2010 Nov 1;112(1-2):1-8. doi: 10.1016/j.drugalcdep.2010.04.021. Epub 2010 Jun 19. — View Citation

Mason GF, Petrakis IL, de Graaf RA, Gueorguieva R, Guidone E, Coric V, Epperson CN, Rothman DL, Krystal JH. Cortical gamma-aminobutyric acid levels and the recovery from ethanol dependence: preliminary evidence of modification by cigarette smoking. Biol Psychiatry. 2006 Jan 1;59(1):85-93. Epub 2005 Nov 14. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Test Day #2 and Test Day #5 - 6 total scans over the period of 2-3 months.
Primary	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.	Test Day #2 and Test Day #5 - 6 total scans over the period of 2-3 months.
Secondary	Symptoms During Nicotine Abstinence (NWSC)	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).	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)
Secondary	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.	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)
Secondary	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.	Day 1 (pre smoking session, day 3 (PM), day 4 (PM), day 5 (pre smoking session)
Secondary	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.	Day 2 (pre and post scan), Day 5 (pre smoking session)
Secondary	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.	Day 2 (pre and post scan), Day 5 (pre smoking session)
Secondary	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.	Day 2 (pre and post scan), Day 5 (pre smoking session)
Secondary	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.	Day 2 (pre and post scan), Day 5 (pre smoking session)
Secondary	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.	Day 2 (pre and post scan), Day 5 (pre smoking session)
Secondary	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.	Day 2 (pre and post scan), Day 5 (pre smoking session)
Secondary	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.	Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)
Secondary	Visual Analog Scale (VAS) Question: Hunger	Visual Analog Scale (VAS) question: Hunger. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.	Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)
Secondary	Visual Analog Scale (VAS) Question: Nauseous	Visual Analog Scale (VAS) question: Nauseous. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.	Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)
Secondary	Visual Analog Scale (VAS) Question: Heartburn.	Visual Analog Scale (VAS) question: Heartburn. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.	Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)
Secondary	Visual Analog Scale (VAS) Question: Tired	Visual Analog Scale (VAS) question: Tired. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.	Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)
Secondary	Visual Analog Scale (VAS) Question: Irritable	Visual Analog Scale (VAS) question: Irritable. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.	Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)
Secondary	Visual Analog Scale (VAS) Question: Energetic	Visual Analog Scale (VAS) question: Energetic. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.	Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)
Secondary	Visual Analog Scale (VAS) Question: Relaxed	Visual Analog Scale (VAS) question: Relaxed. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.	Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)
Secondary	Visual Analog Scale (VAS) Question: Talkative	Visual Analog Scale (VAS) question: Headache. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.	Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)
Secondary	Visual Analog Scale (VAS) Question: Happy	Visual Analog Scale (VAS) question: Happy. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.	Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)
Secondary	Visual Analog Scale (VAS) Question: Nervous	Visual Analog Scale (VAS) question: Nervous. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.	Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)
Secondary	Visual Analog Scale (VAS) Question: Sad	Visual Analog Scale (VAS) question: Sad. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.	Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)
Secondary	Visual Analog Scale (VAS) Question: Calm	Visual Analog Scale (VAS) question: Calm. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.	Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)
Secondary	Visual Analog Scale (VAS) Question: Depressed	Visual Analog Scale (VAS) question: Depressed. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.	Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)
Secondary	Visual Analog Scale (VAS) Question: Drowsy	Visual Analog Scale (VAS) question: Drowsy. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.	Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)
Secondary	Visual Analog Scale (VAS) Question: Anxious	Visual Analog Scale (VAS) question: Anxious. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.	Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)
Secondary	Positive and Negative Affect Schedule (PANAS) Negative Affect	Positive and Negative Affect Schedule (PANAS) Negative Affect Score. Ranges from 10-50 with higher scores representing higher levels of 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)
Secondary	Positive and Negative Affect Schedule (PANAS) Positive Affect	Positive and Negative Affect Schedule (PANAS) Positive Affect Score. Ranges from 10-50 with higher scores representing higher levels of 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)
Secondary	Nicotine Effects Questionnaire (NEQ) Question: Feels Strength of Nicotine	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.	Day 1 (pre smoking session), Day 5 (post smoking session)
Secondary	Nicotine Effects Questionnaire (NEQ) Question: Feels Good Effects of Nicotine	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.	Day 1 (pre smoking session), Day 5 (post smoking session)
Secondary	Nicotine Effects Questionnaire (NEQ) Question: Feels Bad Effects of Nicotine	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.	Day 1 (pre smoking session), Day 5 (post smoking session)
Secondary	Nicotine Effects Questionnaire (NEQ) Question: Head Rush	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.	Day 1 (pre smoking session), Day 5 (post smoking session)

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