Nicotine DependencePhase 4NCT01954966
Progesterone and Brain Imaging Study
A Phase 4 study testing Progesterone in people with Nicotine Dependence and Nicotine Withdrawal, run by University of Pennsylvania at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Nicotine Dependence, Nicotine Withdrawal
- What is being tested?
- Progesterone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 81 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2010to Dec 2021
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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).
Trial locations and contacts
1 site in 1 country.
United States1 site
Penn Center for Women's Behavioral Wellness
Philadelphia, Pennsylvania, 19104
About this study
Official title: Multimodal Imaging of Progesterone/Neurosteroid Effects in Nicotine Addiction
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.
Read the 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.
- Conditions
- Nicotine Dependence, Nicotine Withdrawal
- Being tested
- Progesterone, Placebo
- Keywords
- Nicotine, Smoking
- Medical subject headings
- Tobacco Use Disorder, Smoking
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ProgesteroneDrug
Also called Prometrium
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.
| Study group | Role | What they receive |
|---|---|---|
| Progesterone 200 mg capsules | Active comparator | Subjects will be prescribed progesterone 200 mg capsules by the study Principal Investigator. Subjects will take 200 mg of progesterone daily for four days. Receives: Drug: Progesterone |
| Progesterone 200 mg look-alike capsules | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Test Day #2 and Test Day #5 - 6 total scans over the period of 2-3 months.
Secondary outcomes (31)
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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Visual Analog Scale (VAS) question: Hunger. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.
Measured: 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
Visual Analog Scale (VAS) question: Nauseous. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.
Measured: 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.
Visual Analog Scale (VAS) question: Heartburn. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.
Measured: 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
Visual Analog Scale (VAS) question: Tired. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.
Measured: 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
Visual Analog Scale (VAS) question: Irritable. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.
Measured: 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
Visual Analog Scale (VAS) question: Energetic. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.
Measured: 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
Visual Analog Scale (VAS) question: Relaxed. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.
Measured: 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: Talkative
Visual Analog Scale (VAS) question: Headache. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.
Measured: 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
Visual Analog Scale (VAS) question: Happy. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.
Measured: 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
Visual Analog Scale (VAS) question: Nervous. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.
Measured: 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
Visual Analog Scale (VAS) question: Sad. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.
Measured: 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
Visual Analog Scale (VAS) question: Calm. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.
Measured: 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
Visual Analog Scale (VAS) question: Depressed. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.
Measured: 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
Visual Analog Scale (VAS) question: Drowsy. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.
Measured: 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
Visual Analog Scale (VAS) question: Anxious. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling.
Measured: 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
Positive and Negative Affect Schedule (PANAS) Negative Affect Score. Ranges from 10-50 with higher scores representing higher levels of negative affect.
Measured: 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
Positive and Negative Affect Schedule (PANAS) Positive Affect Score. Ranges from 10-50 with higher scores representing higher levels of positive affect.
Measured: 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)
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.
Measured: Day 1 (pre smoking session), Day 5 (post smoking session)
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.
Measured: Day 1 (pre smoking session), Day 5 (post smoking session)
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.
Measured: Day 1 (pre smoking session), Day 5 (post smoking session)
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.
Measured: Day 1 (pre smoking session), Day 5 (post smoking session)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2013 (estimated)
- Study startNov 2010
- Primary completionDec 2021
- Study completionDec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Nicotine DependenceStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 81 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor
- Investigators
- Cynthia N Epperson, M.D., Principal investigator, Associate Professor of Psychiatry, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01954966
- Sponsor's protocol ID
- 811940
- Other IDs
- K24DA030301
- Status last verified
- Jun 2022
- First submitted
- 6 Nov 2012
- Last updated
- 5 Jul 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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. doi: 10.1016/j.biopsych.2004.09.021.
PubMed 15607299Cai 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 (1)H-MRS study. Neuropsychopharmacology. 2012 Dec;37(13):2764-71. doi: 10.1038/npp.2012.142. Epub 2012 Aug 8.
PubMed 22871916Epperson 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.
PubMed 20561758Mason 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. doi: 10.1016/j.biopsych.2005.06.009. Epub 2005 Nov 14.
PubMed 16289397Cosgrove 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. doi: 10.2967/jnumed.107.042317. Epub 2007 Sep 14.
PubMed 17873128Novick AM, Duffy KA, Johnson RL, Sammel MD, Cao W, Strasser AA, Sofuoglu M, Kuzma A, Loughead J, Morrow AL, Epperson CN. Effect of progesterone administration in male and female smokers on nicotine withdrawal and neural response to smoking cues: role of progesterone conversion to allopregnanolone. Biol Sex Differ. 2022 Oct 23;13(1):60. doi: 10.1186/s13293-022-00472-w.
PubMed 36274158Novick AM, Duffy KA, Johnson RL, Sammel MD, Cao W, Strasser AA, Sofuoglu M, Kuzma A, Loughead J, Epperson CN. Progesterone Increases Nicotine Withdrawal and Anxiety in Male but Not Female Smokers During Brief Abstinence. Nicotine Tob Res. 2022 Nov 12;24(12):1898-1905. doi: 10.1093/ntr/ntac146.
PubMed 35713950
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multimodal Imaging of Progesterone/Neurosteroid Effects in Nicotine Addiction
- ClinicalTrials.gov ID
- NCT01954966
- Acronym / sponsor ID
- 811940
- Conditions
- Nicotine Dependence, Nicotine Withdrawal
- Keywords
- Nicotine, Smoking
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 81 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- Nov 2010 (actual)
- Primary completion
- Dec 2021 (actual)
- Study completion
- Dec 2021 (actual)
- First posted
- 7 Oct 2013 (estimated)
- Results
- Posted 5 Jul 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Progesterone 200 mg capsules | Active comparator | Drug: ProgesteroneSubjects 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 comparator | Drug: PlaceboSubjects 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. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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);
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ProgesteroneAlso: PrometriumParticipants will consume four pills of Progesterone over a period of four days. Participants will be asked to remain abstinent from smoking while taking Progesterone. | Drug | Progesterone 200 mg capsules |
| PlaceboParticipants will consume four pills of Placebo over a period of four days. Participants will be asked to remain abstinent from smoking while taking Placebo. | Drug | Progesterone 200 mg look-alike capsules |
Primary outcome
GABA Pre and Post Progesterone Administration (Dorsal Anterior Cingulate Cortex [DACC])
Time frame: 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.
GABA Pre and Post Progesterone Administration (Dorsolateral Pre-Frontal Cortex [DLPFC])
Time frame: 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.
31 secondary outcomes
Symptoms During Nicotine Abstinence (NWSC)
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)
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)
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
Time frame: Day 2 (pre and post scan), Day 5 (pre smoking session)
Profile of Mood States (POMS) Subscale: Depression-Dejection
Time frame: Day 2 (pre and post scan), Day 5 (pre smoking session)
Profile of Mood States (POMS) Subscale: Anger-Hostility
Time frame: Day 2 (pre and post scan), Day 5 (pre smoking session)
Profile of Mood States (POMS) Subscale: Fatigue
Time frame: Day 2 (pre and post scan), Day 5 (pre smoking session)
Profile of Mood State (POMS) Subscale: Vigor
Time frame: Day 2 (pre and post scan), Day 5 (pre smoking session)
Profile of Mood States (POMS) Subscale: Confusion-Bewilderment
Time frame: Day 2 (pre and post scan), Day 5 (pre smoking session)
Visual Analog Scale (VAS) Question: Headache
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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: Talkative
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
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)
Positive and Negative Affect Schedule (PANAS) Positive Affect
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)
Nicotine Effects Questionnaire (NEQ) Question: Feels Strength of Nicotine
Time frame: Day 1 (pre smoking session), Day 5 (post smoking session)
Nicotine Effects Questionnaire (NEQ) Question: Feels Good Effects of Nicotine
Time frame: Day 1 (pre smoking session), Day 5 (post smoking session)
Nicotine Effects Questionnaire (NEQ) Question: Feels Bad Effects of Nicotine
Time frame: Day 1 (pre smoking session), Day 5 (post smoking session)
Nicotine Effects Questionnaire (NEQ) Question: Head Rush
Time frame: Day 1 (pre smoking session), Day 5 (post smoking session)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jul 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 15607299Epperson 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. doi: 10.1016/j.biopsych.2004.09.021.
- Background: PubMed 22871916Cai 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 (1)H-MRS study. Neuropsychopharmacology. 2012 Dec;37(13):2764-71. doi: 10.1038/npp.2012.142. Epub 2012 Aug 8.
- Background: PubMed 20561758Epperson 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.
- Background: PubMed 16289397Mason 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. doi: 10.1016/j.biopsych.2005.06.009. Epub 2005 Nov 14.
- Background: PubMed 17873128Cosgrove 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. doi: 10.2967/jnumed.107.042317. Epub 2007 Sep 14.
- Derived from this study: PubMed 36274158Novick AM, Duffy KA, Johnson RL, Sammel MD, Cao W, Strasser AA, Sofuoglu M, Kuzma A, Loughead J, Morrow AL, Epperson CN. Effect of progesterone administration in male and female smokers on nicotine withdrawal and neural response to smoking cues: role of progesterone conversion to allopregnanolone. Biol Sex Differ. 2022 Oct 23;13(1):60. doi: 10.1186/s13293-022-00472-w.
- Derived from this study: PubMed 35713950Novick AM, Duffy KA, Johnson RL, Sammel MD, Cao W, Strasser AA, Sofuoglu M, Kuzma A, Loughead J, Epperson CN. Progesterone Increases Nicotine Withdrawal and Anxiety in Male but Not Female Smokers During Brief Abstinence. Nicotine Tob Res. 2022 Nov 12;24(12):1898-1905. doi: 10.1093/ntr/ntac146.
- Center WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Cynthia N Epperson, M.D. principal investigator
Associate Professor of Psychiatry, University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Progesterone in people with Nicotine Dependence and Nicotine Withdrawal, run by University of Pennsylvania at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Jul 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
GABA Pre and Post Progesterone Administration (Dorsal Anterior Cingulate Cortex [DACC]) (time frame: Test Day #2 and Test Day #5 - 6 total scans over the period of 2-3 months.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01954966, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jul 2022.