Multimodal Imaging of Progesterone/Neurosteroid Effects in Nicotine Addiction
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 81
- 试验地点
- 1
- 主要终点
- GABA Pre and Post Progesterone Administration (Dorsolateral Pre-Frontal Cortex [DLPFC])
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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).
研究组 & 干预措施
Progesterone 200 mg capsules
Subjects will be prescribed progesterone 200 mg capsules by the study Principal Investigator. Subjects will take 200 mg of progesterone daily for four days.
干预措施: Progesterone (Drug)
Progesterone 200 mg look-alike capsules
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.
干预措施: Placebo (Drug)
结局指标
主要结局
GABA Pre and Post Progesterone Administration (Dorsolateral Pre-Frontal Cortex [DLPFC])
时间窗: 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])
时间窗: 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.
次要结局
- Profile of Mood States (POMS) Subscale: Anger-Hostility(Day 2 (pre and post scan), Day 5 (pre smoking session))
- 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))
- 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))
- 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))
- 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))
- 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: Sad(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(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 Good Effects of Nicotine(Day 1 (pre smoking session), Day 5 (post smoking session))
- Nicotine Effects Questionnaire (NEQ) Question: Feels Bad Effects of Nicotine(Day 1 (pre smoking session), Day 5 (post smoking session))
- 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))
- Profile of Mood States (POMS) Subscale: Fatigue(Day 2 (pre and post scan), Day 5 (pre smoking session))
- Profile of Mood States (POMS) Subscale: Confusion-Bewilderment(Day 2 (pre and post scan), Day 5 (pre smoking session))
- 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: 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: 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: 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: Happy(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(Day 1 (pre smoking session), Day 5 (post smoking session))
- Nicotine Effects Questionnaire (NEQ) Question: Head Rush(Day 1 (pre smoking session), Day 5 (post smoking session))
- Profile of Mood State (POMS) Subscale: Vigor(Day 2 (pre and post scan), Day 5 (pre smoking session))
- 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: 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: 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: 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: 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: 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: Drowsy(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(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))