Trial Outcomes & Findings for Mapping Brain Glutamate in Humans: Sex Differences in Cigarette Smokers (NCT NCT05279053)
NCT ID: NCT05279053
Last Updated: 2026-03-20
Results Overview
Estrogen concentration measured in serum from blood samples drawn prior to MRS (women only).
Recruitment status
COMPLETED
Target enrollment
58 participants
Primary outcome timeframe
Sampling performed on same day as MRS (before smoking).
Results posted on
2026-03-20
Participant Flow
Recruitment occurred from April 1, 2021 through March 31, 2023. Potential subjects were self-identified as smokers or nonsmokers, and recruited via online and print media, (e.g. Craigslist). Flyers were posted in the UCLA campus. Advertisements are designed to attract smokers interested in participation in research on smoking in exchange for monetary compensation.
Of 58 participants who gave informed consent, 49 completed assessments and provided usable data. The others had issues in attrition or quality control of MRS measurements.
Participant milestones
| Measure |
Male
1. Sex/gender: self-identified as only male
2. Age: 18-70 years of age (children \< 18 years of age will be excluded because of the low prevalence of smoking in this age group (CDC, 2016b), with daily smoking very rare)
3. Language: Participants must speak English fluently, as 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 administered
4. Generally good health without cardiovascular, hepatic, renal, or autoimmune diseases; diabetes; or cancer
5. Smoking history: must have smoked for at least 1 year, endorse inhaling while smoking; smoke on a daily basis; have an expired CO \>10 ppm and urinary cotinine of at least 100 ng/ml at screening/ intake; 6) Meeting DSM 5 criteria for Tobacco Use Disorder.
|
Female
1. Sex/gender: self-identified as only female
2. Age: 18-70 years of age (children \< 18 years of age will be excluded because of the low prevalence of smoking in this age group (CDC, 2016b), with daily smoking very rare)
3. Language: Participants must speak English fluently, as 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 administered
4. Generally good health without cardiovascular, hepatic, renal, or autoimmune diseases; diabetes; or cancer
5. Smoking history: must have smoked for at least 1 year, endorse inhaling while smoking; smoke on a daily basis; have an expired CO \>10 ppm and urinary cotinine of at least 100ng/ml at screening/ intake; 6) Meeting DSM 5 criteria for Tobacco Use Disorder.
|
|---|---|---|
|
Overall Study
STARTED
|
36
|
22
|
|
Overall Study
COMPLETED
|
31
|
18
|
|
Overall Study
NOT COMPLETED
|
5
|
4
|
Reasons for withdrawal
| Measure |
Male
1. Sex/gender: self-identified as only male
2. Age: 18-70 years of age (children \< 18 years of age will be excluded because of the low prevalence of smoking in this age group (CDC, 2016b), with daily smoking very rare)
3. Language: Participants must speak English fluently, as 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 administered
4. Generally good health without cardiovascular, hepatic, renal, or autoimmune diseases; diabetes; or cancer
5. Smoking history: must have smoked for at least 1 year, endorse inhaling while smoking; smoke on a daily basis; have an expired CO \>10 ppm and urinary cotinine of at least 100 ng/ml at screening/ intake; 6) Meeting DSM 5 criteria for Tobacco Use Disorder.
|
Female
1. Sex/gender: self-identified as only female
2. Age: 18-70 years of age (children \< 18 years of age will be excluded because of the low prevalence of smoking in this age group (CDC, 2016b), with daily smoking very rare)
3. Language: Participants must speak English fluently, as 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 administered
4. Generally good health without cardiovascular, hepatic, renal, or autoimmune diseases; diabetes; or cancer
5. Smoking history: must have smoked for at least 1 year, endorse inhaling while smoking; smoke on a daily basis; have an expired CO \>10 ppm and urinary cotinine of at least 100ng/ml at screening/ intake; 6) Meeting DSM 5 criteria for Tobacco Use Disorder.
|
|---|---|---|
|
Overall Study
Attrition/QC of MRS data
|
5
|
4
|
Baseline Characteristics
Numbers in row can be smaller than overall because of quality control.
Baseline characteristics by cohort
| Measure |
Male
n=36 Participants
1. Sex/gender: self-identified as male
2. Age: 18-70 years of age (children \< 18 years of age will be excluded because of the low prevalence of smoking in this age group (CDC, 2016b), with daily smoking very rare)
3. Language: Participants must speak English fluently, as 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 administered
4. Generally good health without cardiovascular, hepatic, renal, or autoimmune diseases; diabetes; or cancer
5. Smoking history: must have smoked for at least 1 year, endorse inhaling while smoking; smoke on a daily basis; have an expired CO \>10 ppm and urinary cotinine of at least 100ng/ml at screening/ intake; 6) Meeting DSM 5 criteria for Tobacco Use Disorder.
|
Female
n=22 Participants
1. Sex/gender: self-identified as female
2. Age: 18-55 years of age (to age-match with smokers)
3. Language: Participants must speak English fluently, as 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 administered
4. Generally good health without cardiovascular, hepatic, renal, or autoimmune diseases; diabetes; or cancer.
|
Total
n=58 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
32 years
STANDARD_DEVIATION 6 • n=36 Participants
|
34 years
STANDARD_DEVIATION 8 • n=22 Participants
|
33 years
STANDARD_DEVIATION 6 • n=58 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=36 Participants
|
22 Participants
n=22 Participants
|
22 Participants
n=58 Participants
|
|
Sex: Female, Male
Male
|
36 Participants
n=36 Participants
|
0 Participants
n=22 Participants
|
36 Participants
n=58 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
5 Participants
n=36 Participants
|
4 Participants
n=22 Participants
|
9 Participants
n=58 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
27 Participants
n=36 Participants
|
17 Participants
n=22 Participants
|
44 Participants
n=58 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
4 Participants
n=36 Participants
|
1 Participants
n=22 Participants
|
5 Participants
n=58 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=36 Participants
|
0 Participants
n=22 Participants
|
1 Participants
n=58 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=36 Participants
|
1 Participants
n=22 Participants
|
3 Participants
n=58 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=36 Participants
|
0 Participants
n=22 Participants
|
1 Participants
n=58 Participants
|
|
Race (NIH/OMB)
Black or African American
|
11 Participants
n=36 Participants
|
5 Participants
n=22 Participants
|
16 Participants
n=58 Participants
|
|
Race (NIH/OMB)
White
|
15 Participants
n=36 Participants
|
11 Participants
n=22 Participants
|
26 Participants
n=58 Participants
|
|
Race (NIH/OMB)
More than one race
|
2 Participants
n=36 Participants
|
5 Participants
n=22 Participants
|
7 Participants
n=58 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
4 Participants
n=36 Participants
|
0 Participants
n=22 Participants
|
4 Participants
n=58 Participants
|
|
Region of Enrollment
United States
|
36 Participants
n=36 Participants
|
22 Participants
n=22 Participants
|
58 Participants
n=58 Participants
|
|
Glutamate in dorsal anterior cingulate
|
7.96 Institutional Units
STANDARD_DEVIATION 1.72 • n=23 Participants • Numbers in row can be smaller than overall because of quality control.
|
6.85 Institutional Units
STANDARD_DEVIATION 1.50 • n=15 Participants • Numbers in row can be smaller than overall because of quality control.
|
7.52 Institutional Units
STANDARD_DEVIATION 1.65 • n=38 Participants • Numbers in row can be smaller than overall because of quality control.
|
|
Glutamate in the insula
|
7.54 Institutional Units
STANDARD_DEVIATION 1.16 • n=24 Participants • Numbers in row can be smaller than overall because of quality control.
|
7.12 Institutional Units
STANDARD_DEVIATION 1.16 • n=15 Participants • Numbers in row can be smaller than overall because of quality control.
|
7.38 Institutional Units
STANDARD_DEVIATION 1.18 • n=39 Participants • Numbers in row can be smaller than overall because of quality control.
|
|
Glutamate in whole brain
|
5.70 Institutional Units
STANDARD_DEVIATION 1.12 • n=23 Participants • Numbers in row can be smaller than overall because of quality control.
|
5.52 Institutional Units
STANDARD_DEVIATION 1.03 • n=15 Participants • Numbers in row can be smaller than overall because of quality control.
|
5.63 Institutional Units
STANDARD_DEVIATION 1.09 • n=38 Participants • Numbers in row can be smaller than overall because of quality control.
|
PRIMARY outcome
Timeframe: Measured before and after smoking a cigarette by both groups (men and women). Group means below reflect overall group means averaged across time points as reported from descriptive statistics in the Generalized Linear Mixed Model.Population: Analysis population included all participants who provided MRS data that met quality control criteria. For this endpoint, 18 females and 24 males had data that met quality control criteria.
Glutamate levels, as measured using MRS, in the dorsal anterior cingulate cortex.
Outcome measures
| Measure |
Male
n=24 Participants
1. Sex/gender: self-identified as only male
2. Age: 18-70 years of age (children \< 18 years of age will be excluded because of the low prevalence of smoking in this age group (CDC, 2016b), with daily smoking very rare)
3. Language: Participants must speak English fluently, as 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 administered
4. Generally good health without cardiovascular, hepatic, renal, or autoimmune diseases; diabetes; or cancer
5. Smoking history: must have smoked for at least 1 year, endorse inhaling while smoking; smoke on a daily basis; have an expired CO \>10 ppm and urinary cotinine of at least 100ng/ml at screening/ intake; 6) Meeting DSM 5 criteria for Tobacco Use Disorder.
|
Female
n=18 Participants
1. Sex/gender: self-identified as only female
2. Age: 18-70 years of age (children \< 18 years of age will be excluded because of the low prevalence of smoking in this age group (CDC, 2016b), with daily smoking very rare)
3. Language: Participants must speak English fluently, as 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 administered
4. Generally good health without cardiovascular, hepatic, renal, or autoimmune diseases; diabetes; or cancer
5. Smoking history: must have smoked for at least 1 year, endorse inhaling while smoking; smoke on a daily basis; have an expired CO \>10 ppm and urinary cotinine of at least 100ng/ml at screening/ intake; 6) Meeting DSM 5 criteria for Tobacco Use Disorder.
|
|---|---|---|
|
Glutamate in the Dorsal Anterior Cingulate Cortex
|
8.11 Institutional Units
Standard Deviation 1.71
|
7.05 Institutional Units
Standard Deviation 1.61
|
PRIMARY outcome
Timeframe: Measured before and after smoking a cigarette by both groups (men and women). Group means below reflect overall group means averaged across time points as reported from descriptive statistics in the Generalized Linear Mixed Model.Population: Analysis population included all participants who provided MRS data that met quality control criteria. For this endpoint, 18 females and 25 males had data that met quality control criteria.
Glutamate levels, as measured using MRS, in the insula.
Outcome measures
| Measure |
Male
n=25 Participants
1. Sex/gender: self-identified as only male
2. Age: 18-70 years of age (children \< 18 years of age will be excluded because of the low prevalence of smoking in this age group (CDC, 2016b), with daily smoking very rare)
3. Language: Participants must speak English fluently, as 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 administered
4. Generally good health without cardiovascular, hepatic, renal, or autoimmune diseases; diabetes; or cancer
5. Smoking history: must have smoked for at least 1 year, endorse inhaling while smoking; smoke on a daily basis; have an expired CO \>10 ppm and urinary cotinine of at least 100ng/ml at screening/ intake; 6) Meeting DSM 5 criteria for Tobacco Use Disorder.
|
Female
n=18 Participants
1. Sex/gender: self-identified as only female
2. Age: 18-70 years of age (children \< 18 years of age will be excluded because of the low prevalence of smoking in this age group (CDC, 2016b), with daily smoking very rare)
3. Language: Participants must speak English fluently, as 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 administered
4. Generally good health without cardiovascular, hepatic, renal, or autoimmune diseases; diabetes; or cancer
5. Smoking history: must have smoked for at least 1 year, endorse inhaling while smoking; smoke on a daily basis; have an expired CO \>10 ppm and urinary cotinine of at least 100ng/ml at screening/ intake; 6) Meeting DSM 5 criteria for Tobacco Use Disorder.
|
|---|---|---|
|
Glutamate in the Insula
|
7.44 Institutional Units
Standard Deviation 1.33
|
6.98 Institutional Units
Standard Deviation 1.36
|
PRIMARY outcome
Timeframe: Measured before and after smoking a cigarette by both groups (men and women). Group means below reflect overall group means averaged across time points as reported from descriptive statistics in the Generalized Linear Mixed Model.Population: Analysis population includes all participants whose data met quality control criteria.
Glutamate measured using the MRS echoplanar spectroscopic imaging in abstinent smokers.
Outcome measures
| Measure |
Male
n=24 Participants
1. Sex/gender: self-identified as only male
2. Age: 18-70 years of age (children \< 18 years of age will be excluded because of the low prevalence of smoking in this age group (CDC, 2016b), with daily smoking very rare)
3. Language: Participants must speak English fluently, as 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 administered
4. Generally good health without cardiovascular, hepatic, renal, or autoimmune diseases; diabetes; or cancer
5. Smoking history: must have smoked for at least 1 year, endorse inhaling while smoking; smoke on a daily basis; have an expired CO \>10 ppm and urinary cotinine of at least 100ng/ml at screening/ intake; 6) Meeting DSM 5 criteria for Tobacco Use Disorder.
|
Female
n=18 Participants
1. Sex/gender: self-identified as only female
2. Age: 18-70 years of age (children \< 18 years of age will be excluded because of the low prevalence of smoking in this age group (CDC, 2016b), with daily smoking very rare)
3. Language: Participants must speak English fluently, as 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 administered
4. Generally good health without cardiovascular, hepatic, renal, or autoimmune diseases; diabetes; or cancer
5. Smoking history: must have smoked for at least 1 year, endorse inhaling while smoking; smoke on a daily basis; have an expired CO \>10 ppm and urinary cotinine of at least 100ng/ml at screening/ intake; 6) Meeting DSM 5 criteria for Tobacco Use Disorder.
|
|---|---|---|
|
Glutamate in Whole Brain (Gray Matter Plus White Matter).
|
5.65 Institutional Units
Standard Deviation 1.01
|
5.53 Institutional Units
Standard Deviation 1.02
|
PRIMARY outcome
Timeframe: Sampling performed on same day as MRS (before smoking).Population: Analysis population comprises participants who had MRS measurement that passed quality control and blood sampled for hormone assay.
Estrogen concentration measured in serum from blood samples drawn prior to MRS (women only).
Outcome measures
| Measure |
Male
n=13 Participants
1. Sex/gender: self-identified as only male
2. Age: 18-70 years of age (children \< 18 years of age will be excluded because of the low prevalence of smoking in this age group (CDC, 2016b), with daily smoking very rare)
3. Language: Participants must speak English fluently, as 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 administered
4. Generally good health without cardiovascular, hepatic, renal, or autoimmune diseases; diabetes; or cancer
5. Smoking history: must have smoked for at least 1 year, endorse inhaling while smoking; smoke on a daily basis; have an expired CO \>10 ppm and urinary cotinine of at least 100ng/ml at screening/ intake; 6) Meeting DSM 5 criteria for Tobacco Use Disorder.
|
Female
1. Sex/gender: self-identified as only female
2. Age: 18-70 years of age (children \< 18 years of age will be excluded because of the low prevalence of smoking in this age group (CDC, 2016b), with daily smoking very rare)
3. Language: Participants must speak English fluently, as 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 administered
4. Generally good health without cardiovascular, hepatic, renal, or autoimmune diseases; diabetes; or cancer
5. Smoking history: must have smoked for at least 1 year, endorse inhaling while smoking; smoke on a daily basis; have an expired CO \>10 ppm and urinary cotinine of at least 100ng/ml at screening/ intake; 6) Meeting DSM 5 criteria for Tobacco Use Disorder.
|
|---|---|---|
|
Serum Estrogen
|
92.77 pg/mL
Standard Deviation 65.16
|
—
|
Adverse Events
Male/Smokers and Nonsmokers
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Female/Smokers and Nonsmokers
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Edythe D. London, Ph.D.
UCLA David Geffen School of Medicine
Phone: 3108250606
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place