Mapping Brain Glutamate in Humans: Sex Differences in Cigarette Smokers

Cigarette Smoking Clinical Trial

Official title:

Mapping Brain Glutamate in Humans: Sex Differences in Cigarette Smokers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05279053
• Other study ID #: 17-000387
• Status: Completed
• Start date: April 1, 2021
• Est. completion date: March 31, 2023

Study information

• Verified date: August 2023
• Source: University of California, Los Angeles
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The proposed study will evaluate sex differences in whole-brain glutamate (Glu), with a focus on the dorsal anterior cingulate cortex (dACC), anterior insula, and thalamus, as well as how it is influenced by sex (males vs. females), smoking state (overnight abstinent vs. sated), and circulating ovarian hormones (estrogen and progesterone) in women. Glu will be measured in almost the entire brain, with special focus on the dorsal anterior cingulate cortex (dACC), anterior insula, and thalamus, all of which have been implicated in behavioral states linked to tobacco withdrawal, using an echo-planar spectroscopic imaging (EPSI) variant of magnetic resonance spectroscopy (MRS). Serum ovarian hormones (estrogen and progesterone) will be measured for female participants to determine relationships between brain Glu and this hormone. Whole-brain Glu will be measured in 60 smokers (30 men, 30 women) twice, after overnight (~12 h) abstinence and after participants smoke the first cigarette of the day.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 58
• Est. completion date: March 31, 2023
• Est. primary completion date: March 31, 2023
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

1. Self-identified as only male or female

2. Age 18-45 years (children <18 years will be excluded due to low prevalence of conventional cigarette smoking; female participants >45 years of age will be excluded to avoid effects of perimenopause and menopause in women; male participants >45 years of age will be excluded as well to ensure that male and female groups are matched on age

3. English fluency demonstrated by verbal skills sufficient to participate in a conversation, including the ability to ask and answer questions at a level that assures adequate understanding of the study (a comprehension quiz will be given)

4. Right handedness (evaluated using the Edinburgh Inventory)

5. Generally in good health without cardiovascular, hepatic, renal, or autoimmune diseases, diabetes, or cancer

6. Must have smoked for =1 year

7. Must endorse inhaling while smoking

8. Must smoke =10 cigarettes per day

9. Must have expired CO >10 ppm and urinary cotinine =100 ng/ml at screening/intake

10. Fulfillment of DSM-5 criteria for Tobacco Use Disorder

Exclusion Criteria:

1. Seeking treatment for nicotine dependence within 3 months of screening

2. Medical condition that may compromise safety (based on history, physical exam)

3. Neurological disorder that would compromise compliance and/or informed consent

4. Major psychiatric disorder (e.g., Major Depression, Schizophrenia, Bipolar Disorder) per DSM-5 MINI

5. Current drug use disorders other than Tobacco Use Disorder (as defined in DSM-5)

6. Recent use of cocaine, opiates, benzodiazepines, or amphetamines as shown by urine test at the screening or testing sessions

7. Smoke marijuana >3X/week (self-report) or positive marijuana urine test on a scan day (positive at screening allowed)

8. Use of tobacco in forms other than cigarettes (e.g., snuff, chewing tobacco, e-cigarettes) >10 days in the month before screening

9. Preference for menthol cigarettes, given sex differences in the effect of menthol on the rate of nicotine entry into the brain

10. Pregnancy or nursing

11. Presence in the body of metal that would compromise safety during MRI

12. Claustrophobia

13. Any other condition that would compromise safety

Related Conditions & MeSH terms

• Cigarette Smoking
• Sex
• Tobacco Dependence
• Tobacco Use Disorder

Locations

Country	Name	City	State
United States	UCLA Semel Institute	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, Los Angeles

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Circulating Ovarian Hormone: Estrogen - in overnight abstinent smokers	Estrogen assayed via a blood sample	Measured before and after smoking a cigarette across a period of 2 hours
Primary	Circulating Ovarian Hormone: Progesterone - in overnight abstinent smokers	Estrogen assayed via a blood sample	Measured before and after smoking a cigarette across a period of 2 hours
Primary	Whole Brain Glutamate	Measured by EPSI acquisition in overnight abstinent smokers	Measured before and after smoking a cigarette across a period of 2 hours
Primary	Nicotine Metabolite Ratio	Measured by blood sample	Measured before smoking a cigarette at a single timepoint
Secondary	Urge to Smoke Scale (UTS)	This is a 10-item self-reporting questionnaire that measures cigarette craving	Measured before and after smoking a cigarette across a period of 2 hours
Secondary	Shiffman-Jarvik Withdrawal Scale (SJWS)	This is a 25-item self-reporting questionnaire that measures psychological withdrawal	Measured before and after smoking a cigarette across a period of 2 hours
Secondary	Positive and Negative Affect Schedule (PANAS)	This is a 20-item self-reporting questionnaire that measures positive and negative affect	Measured before and after smoking a cigarette across a period of 2 hours
Secondary	Spielberger State-Trait Anxiety (STAI)	This is a 20-item self-reporting questionnaire that measures anxiety	Measured before and after smoking a cigarette across a period of 2 hours