Progesterone and Brain Imaging Study

NCT01954966 | Completed Phase 4 Results DMC

• 2 other identifiers: 811940K24DA030301
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 1

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.

Conditions

Nicotine Dependence; Nicotine Withdrawal

Keywords

Nicotine; Smoking

Outcome Measures

Primary Outcomes (2)

• 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.

• 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 Outcomes (31)

• 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)

• 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)

• Tiffany Questionnaire on Smoking Urges (TQSU)

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

• 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: Depression-Dejection

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

Study Arms (2)

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.

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.

Drug: Placebo

Interventions

Progesterone DRUG

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.

Also known as: Prometrium

Progesterone 200 mg capsules

Placebo DRUG

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.

Progesterone 200 mg look-alike capsules

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Female and male smokers, aged 18 to 50 years;
• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• University of Pennsylvania: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Penn Center for Women's Behavioral Wellness

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (7)

• 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.

  PMID: 15607299 BACKGROUND

• 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 (1)H-MRS study. Neuropsychopharmacology. 2012 Dec;37(13):2764-71. doi: 10.1038/npp.2012.142. Epub 2012 Aug 8.

  PMID: 22871916 BACKGROUND

• 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.

  PMID: 20561758 BACKGROUND

• 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. doi: 10.1016/j.biopsych.2005.06.009. Epub 2005 Nov 14.

  PMID: 16289397 BACKGROUND

• 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. doi: 10.2967/jnumed.107.042317. Epub 2007 Sep 14.

  PMID: 17873128 BACKGROUND

• Novick 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.

  PMID: 36274158 DERIVED

• Novick 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.

  PMID: 35713950 DERIVED

Related Links

• Center Website

MeSH Terms

Conditions

Tobacco Use Disorder; Smoking

Interventions

Progesterone

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Behavior

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Corpus Luteum Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progesterone Congeners; Gonadal Steroid Hormones

Results Point of Contact

• Title: Claudia Iannelli
• Organization: University of Pennsylvania

Claudia.iannelli@pennmedicine.upenn.edu

6104424426

Study Officials

• Cynthia N Epperson, M.D.

  Associate Professor of Psychiatry, University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2012
• First Posted: October 7, 2013
• Study Start: November 1, 2010
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2021
• Last Updated: July 5, 2022
• Results First Posted: July 5, 2022

Record last verified: 2022-06

Locations

US (1)