Cognitive Training for Nicotine Dependence

• Sponsor: University of Pennsylvania (Other)
• Overall Status: Completed
• CT.gov ID: NCT01252966
• Collaborator: (none)
• Enrollment: 213
• Location: 1
• Arms: 2
• Duration (Months): 54
• Patients Per Site Per Month: 3.9

Study Details

Study Description

Brief Summary

This randomized clinical trial tested the effects of a computerized (web-based) cognitive training intervention on smoking cessation.

All participants received 8 weeks of standard nicotine patch therapy, smoking cessation counseling, and were randomized to 1 of 2 different training programs: cognitive training vs. control training.

Condition or Disease	Intervention/Treatment	Phase
Tobacco Use Disorder; Nicotine Addiction	Behavioral: Cognitive Training; Behavioral: Control training	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 213 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Cognitive Training for Nicotine Dependence
• Study Start Date: Mar 1, 2011
• Actual Primary Completion Date: Sep 1, 2015
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cognitive Training Participants in this arm received computerized cognitive training in addition to nicotine patch and smoking cessation counseling.	Behavioral: Cognitive Training; The computerized cognitive training intervention is a 12-week standardized course of internet-based computerized cognitive exercises designed to enhance executive cognitive function.
Placebo Comparator: Control Training Participants in this arm received computerized control training in addition to nicotine patch and smoking cessation counseling	Behavioral: Control training; The computerized control training intervention is a 12-week standardized course of internet-based deep breathing exercises which does not contain the cognitive exercises designed to enhance executive cognitive function.

Outcome Measures

Primary Outcome Measures

1. Point-prevalence Abstinence at End of Treatment [End of treatment (Week 12)]

   Daily smoking, from the Target Quit Date to End of Treatment (EOT), was assessed by a validated timeline follow-back measure. Based on guidelines for smoking cessation trials, the primary outcome was 7-day point prevalence abstinence at EOT, and abstinence was defined as no self-reported smoking (even a puff) for at least 7 days, with in-person verification by carbon monoxide breath levels (CO <8ppm). Following standard convention, participants who withdrew or were lost to follow-up were considered smokers.

Secondary Outcome Measures

1. Point-prevalence Abstinence at 6-month Follow-up [6 month follow-up]

   Daily smoking from the Target Quit Date to 6 month follow-up was assessed by a validated timeline follow-back measure. Based on guidelines for smoking cessation trials, the secondary outcome was 7-day point prevalence abstinence at the 6 month follow-up, and abstinence was defined as no self-reported smoking (even a puff) for at least 7 days, with in-person verification by carbon monoxide breath levels (CO <8ppm). Following standard convention, participants who withdrew or were lost to follow-up were considered smokers.

2. Cognitive Performance (Working Memory) [Baseline and Week 12 (EOT)]

   Change in performance on the Digit Span Forward task (working memory) between Baseline and End of Treatment (Week 12). In this task, participants are presented with a series of digits on the computer screen at one second intervals. Participants are then required to enter the digits in order. The number of digits in each series ranges from 3 to 7, and the maximum recall span is the length of the largest series entered correctly. The outcome measure is the change score (calculated by subtracting the Baseline score from the end of treatment score). Change scores can range from -4 to 4. Negative numbers indicate worse performance at EOT; positive numbers indicate better performance at EOT; and 0 indicates no change.

3. Cognitive Performance (Response Inhibition) [Baseline and Week 12 (EOT)]

   Change in performance on the Go/No-Go Task (response inhibition) between Baseline and End of Treatment (Week 12). In this task, participants are presented with a series of stimuli (the word "PRESS" in either green or red). Participants are instructed to respond by pressing the spacebar when the stimulus is green, and to withhold a response when the stimulus is red. The outcome is the change in number of commission errors (failure to withhold a response to a red stimulus) from EOT minus baseline. The potential range for the change score is -42 to 42. Negative numbers indicate a decrease in the number of commission errors (improved performance) from baseline to EOT; positive numbers indicate an increase in commission errors (worse performance); 0 indicates no change.

4. Cognitive Performance (Attention) [Baseline and Week 12 (EOT)]

   Change in performance on the Continuous Performance Task (attention) between Baseline and End of Treatment (Week 12). In this task, participants are presented with a series of letters at 2.5s intervals and are instructed to respond by pressing the space bar if the same letter appears twice in a row. The outcome is the change in the number of commission errors (the number of times the participant responded to a non-target at EOT minus baseline). There are a total of 125 trials, with 20 target trials (response required) and 85 non-target trials (no response required); therefore the possible range for the change score is -85 to 85. Negative numbers indicate a decrease in commission errors (better performance at EOT compared to baseline); positive numbers indicate an increase in commission errors (worse performance at EOT compared to baseline); and 0 indicates no change.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion:

1. Healthy male and female treatment-seeking smokers who are between 18 and 65 years of age and self-report smoking at least 5 cigarettes (menthol and/or non-menthol) per day for at least the last 6 months

2. Plan to live in the area for at least the next 8 months

3. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the combined consent and HIPAA form

4. Able to communicate fluently in English (speaking, writing, and reading)

5. Have uninterrupted access to a home computer with sound capabilities, keyboard, mouse, and active Internet connection

6. Provide a Carbon Monoxide (CO) breath test reading greater than or equal to 8 parts per million (ppm) at Intake Visit

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Center for Interdiscplinary Research on Nicotine Addiction, University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• University of Pennsylvania

Investigators

• Principal Investigator: Caryn Lerman, PhD, University of Pennsylvania

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT01252966
• Other Study ID Numbers: 812429
• First Posted: Dec 3, 2010
• Last Update Posted: Jan 16, 2017
• Last Verified: Jan 1, 2017

• Keywords provided by University of Pennsylvania: Tobacco; Smoking; Cognition; Behavioral Training; Relapse
• Additional relevant MeSH terms: Tobacco Use Disorder

Study Results

Participant Flow

Recruitment Details	Recruitment for this clinical trial began in March 2011. Study accrual was completed in September 2015, with a final sample of N=213 in the intention-to-treat (ITT) analysis.
Pre-assignment Detail	Five hundred and fifty-seven participants provided consent and 213 were randomized. Reasons for exclusion from randomization included no home computer or internet access and failure to meet final eligibility criteria at the Intake Visit.

Arm/Group Title	Cognitive Training	Control Training
Arm/Group Description	The Cognitive Training intervention is a 12-week standardized course of internet-based computerized cognitive exercises designed to enhance executive cognitive function. Participants also receive nicotine patch and smoking cessation counseling.	The Control Training intervention is a 12-week standardized course of internet-based deep breathing exercises which does not contain the cognitive exercises designed to enhance executive cognitive function. Participants also receive nicotine patch and smoking cessation counseling.
Period Title: Overall Study
STARTED	108	105
COMPLETED	85	92
NOT COMPLETED	23	13

Baseline Characteristics

Arm/Group Title	Cognitive Training	Control Training	Total
Arm/Group Description	The Cognitive Training intervention is a 12-week standardized course of internet-based computerized cognitive exercises designed to enhance executive cognitive function. Participants also receive nicotine patch and smoking cessation counseling.	The Control Training intervention is a 12-week standardized course of internet-based deep breathing exercises which does not contain the cognitive exercises designed to enhance executive cognitive function. Participants also receive nicotine patch and smoking cessation counseling.	Total of all reporting groups
Overall Participants	108	105	213
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	43.18 (12.62)	43.39 (12.38)	43.28 (12.48)
Gender (Count of Participants)
Female	53 49.1%	54 51.4%	107 50.2%
Male	55 50.9%	51 48.6%	106 49.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 0.9%	5 4.8%	6 2.8%
Not Hispanic or Latino	107 99.1%	100 95.2%	207 97.2%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.9%	0 0%	1 0.5%
Asian	4 3.7%	2 1.9%	6 2.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	38 35.2%	42 40%	80 37.6%
White	61 56.5%	54 51.4%	115 54%
More than one race	3 2.8%	4 3.8%	7 3.3%
Unknown or Not Reported	1 0.9%	3 2.9%	4 1.9%
Region of Enrollment (participants) [Number]
United States	108 100%	105 100%	213 100%
Cigarettes Per Day (cigarettes smoked per day) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cigarettes smoked per day]	16.42 (6.14)	15.73 (5.23)	16.08 (5.70)
Fagerström Test for Nicotine Dependence Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	4.82 (2.11)	4.65 (1.74)	4.74 (1.94)

Outcome Measures

1. Primary Outcome

Title	Point-prevalence Abstinence at End of Treatment
Description	Daily smoking, from the Target Quit Date to End of Treatment (EOT), was assessed by a validated timeline follow-back measure. Based on guidelines for smoking cessation trials, the primary outcome was 7-day point prevalence abstinence at EOT, and abstinence was defined as no self-reported smoking (even a puff) for at least 7 days, with in-person verification by carbon monoxide breath levels (CO <8ppm). Following standard convention, participants who withdrew or were lost to follow-up were considered smokers.
Time Frame	End of treatment (Week 12)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cognitive Training	Control Training
Arm/Group Description	The Cognitive Training intervention is a 12-week standardized course of internet-based computerized cognitive exercises designed to enhance executive cognitive function. Participants also receive nicotine patch and smoking cessation counseling.	The Control Training intervention is a 12-week standardized course of internet-based deep breathing exercises which does not contain the cognitive exercises designed to enhance executive cognitive function. Participants also receive nicotine patch and smoking cessation counseling.
Measure Participants	108	105
Number [Percentage of participants]	38 35.2%	43 41%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cognitive Training, Control Training
	Comments	Longitudinal logistic regression with fitted generalized estimating equations (GEE) was used to estimate an overall treatment effect odds ratio including both the EOT and 6-month time points and relevant covariates (e.g., baseline smoking rate, age, Shipley IQ score). The study (n=213) had 80% power to detect small to medium effects on quit rates (corresponding to Cohen's one-sample d=0.38).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.14
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.69
	Confidence Interval	(2-Sided) 95%; 0.42 to 1.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Point-prevalence Abstinence at 6-month Follow-up
Description	Daily smoking from the Target Quit Date to 6 month follow-up was assessed by a validated timeline follow-back measure. Based on guidelines for smoking cessation trials, the secondary outcome was 7-day point prevalence abstinence at the 6 month follow-up, and abstinence was defined as no self-reported smoking (even a puff) for at least 7 days, with in-person verification by carbon monoxide breath levels (CO <8ppm). Following standard convention, participants who withdrew or were lost to follow-up were considered smokers.
Time Frame	6 month follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cognitive Training	Control Training
Arm/Group Description	The Cognitive Training intervention is a 12-week standardized course of internet-based computerized cognitive exercises designed to enhance executive cognitive function. Participants also receive nicotine patch and smoking cessation counseling.	The Control Training intervention is a 12-week standardized course of internet-based deep breathing exercises which does not contain the cognitive exercises designed to enhance executive cognitive function. Participants also receive nicotine patch and smoking cessation counseling.
Measure Participants	108	105
Number [Percentage of participants]	15 13.9%	25 23.8%

3. Secondary Outcome

Title	Cognitive Performance (Working Memory)
Description	Change in performance on the Digit Span Forward task (working memory) between Baseline and End of Treatment (Week 12). In this task, participants are presented with a series of digits on the computer screen at one second intervals. Participants are then required to enter the digits in order. The number of digits in each series ranges from 3 to 7, and the maximum recall span is the length of the largest series entered correctly. The outcome measure is the change score (calculated by subtracting the Baseline score from the end of treatment score). Change scores can range from -4 to 4. Negative numbers indicate worse performance at EOT; positive numbers indicate better performance at EOT; and 0 indicates no change.
Time Frame	Baseline and Week 12 (EOT)

Outcome Measure Data

Analysis Population Description

Participants with performance >3SD from the mean at baseline were excluded as outliers.

Arm/Group Title	Cognitive Training	Control Training
Arm/Group Description	The Cognitive Training intervention is a 12-week standardized course of internet-based computerized cognitive exercises designed to enhance executive cognitive function. Participants also receive nicotine patch and smoking cessation counseling.	The Control Training intervention is a 12-week standardized course of internet-based deep breathing exercises which does not contain the cognitive exercises designed to enhance executive cognitive function. Participants also receive nicotine patch and smoking cessation counseling.
Measure Participants	82	92
Mean (Standard Deviation) [Change in maximum recall span]	0.22 (1.2)	0.03 (1.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cognitive Training, Control Training
	Comments	Multiple regression models were used to estimate effects of treatment on change in cognitive performance. Age, Shipley IQ score, number of cigarettes smoked per day at baseline, and EOT smoking status were included as covariates.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.30
	Comments
	Method	Regression, Linear
	Comments

4. Secondary Outcome

Title	Cognitive Performance (Response Inhibition)
Description	Change in performance on the Go/No-Go Task (response inhibition) between Baseline and End of Treatment (Week 12). In this task, participants are presented with a series of stimuli (the word "PRESS" in either green or red). Participants are instructed to respond by pressing the spacebar when the stimulus is green, and to withhold a response when the stimulus is red. The outcome is the change in number of commission errors (failure to withhold a response to a red stimulus) from EOT minus baseline. The potential range for the change score is -42 to 42. Negative numbers indicate a decrease in the number of commission errors (improved performance) from baseline to EOT; positive numbers indicate an increase in commission errors (worse performance); 0 indicates no change.
Time Frame	Baseline and Week 12 (EOT)

Outcome Measure Data

Analysis Population Description

Participants with performance >3SD from the mean at baseline were excluded as outliers.

Arm/Group Title	Cognitive Training	Control Training
Arm/Group Description	The computerized cognitive training intervention is a 12-week standardized course of internet-based computerized cognitive exercises designed to enhance executive cognitive function.	The computerized control training intervention is a 12-week standardized course of internet-based deep breathing exercises which does not contain the cognitive exercises designed to enhance executive cognitive function.
Measure Participants	82	92
Mean (Standard Deviation) [Change in number of commission errors]	-0.84 (2.5)	-0.49 (2.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cognitive Training, Control Training
	Comments	Multiple regression models were used to estimate effects of treatment on change in cognitive performance. Age, Shipley IQ score, number of cigarettes smoked per day at baseline, and EOT smoking status were included as covariates.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.30
	Comments
	Method	Regression, Linear
	Comments

5. Secondary Outcome

Title	Cognitive Performance (Attention)
Description	Change in performance on the Continuous Performance Task (attention) between Baseline and End of Treatment (Week 12). In this task, participants are presented with a series of letters at 2.5s intervals and are instructed to respond by pressing the space bar if the same letter appears twice in a row. The outcome is the change in the number of commission errors (the number of times the participant responded to a non-target at EOT minus baseline). There are a total of 125 trials, with 20 target trials (response required) and 85 non-target trials (no response required); therefore the possible range for the change score is -85 to 85. Negative numbers indicate a decrease in commission errors (better performance at EOT compared to baseline); positive numbers indicate an increase in commission errors (worse performance at EOT compared to baseline); and 0 indicates no change.
Time Frame	Baseline and Week 12 (EOT)

Outcome Measure Data

Analysis Population Description

Participants with performance >3SD from the mean at Baseline were excluded as outliers.

Arm/Group Title	Cognitive Training	Control Training
Arm/Group Description	The Cognitive Training intervention is a 12-week standardized course of internet-based computerized cognitive exercises designed to enhance executive cognitive function. Participants also receive nicotine patch and smoking cessation counseling.	The Control Training intervention is a 12-week standardized course of internet-based deep breathing exercises which does not contain the cognitive exercises designed to enhance executive cognitive function. Participants also receive nicotine patch and smoking cessation counseling.
Measure Participants	82	92
Mean (Standard Deviation) [Change in number of commission errors]	-0.27 (1.3)	0.54 (1.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cognitive Training, Control Training
	Comments	Multiple regression models were used to estimate effects of treatment on change in cognitive performance. Age, Shipley IQ score, number of cigarettes smoked per day at baseline, and EOT smoking status were included as covariates.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.033
	Comments	Results would not survive correction for multiple hypothesis testing.
	Method	Regression, Linear
	Comments

Adverse Events

Time Frame	AE and SAE data were collected from enrollment through follow up (~31 weeks).
Adverse Event Reporting Description	Participants (PPTs) completed an anticipated side effects questionnaire (transdermal nicotine) at Pre-Quit (baseline measure) and at every subsequent in-person visit during the treatment period (systematic assessment). AE and SAE information was collected via spontaneous report from enrollment through follow up as a non-systematic assessment (n=213).
Arm/Group Title	Cognitive Training		Control Training
Arm/Group Description
All Cause Mortality
	Cognitive Training		Control Training
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Cognitive Training		Control Training
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/108 (5.6%)		3/105 (2.9%)
Gastrointestinal disorders
Bowel Blockage	1/108 (0.9%)	1	0/105 (0%)	0
General disorders
Pancreatitis	1/108 (0.9%)	1	0/105 (0%)	0
Infections and infestations
Infection	1/108 (0.9%)	1	0/105 (0%)	0
Reproductive system and breast disorders
Breast Cancer	0/108 (0%)	0	1/105 (1%)	1
Respiratory, thoracic and mediastinal disorders
Collapsed Lung	1/108 (0.9%)	1	0/105 (0%)	0
Skin and subcutaneous tissue disorders
Squamous Cell Carcinoma	1/108 (0.9%)	1	0/105 (0%)	0
Surgical and medical procedures
Emergency Procedure	1/108 (0.9%)	1	0/105 (0%)	0
Surgery (Gastric Bypass)	0/108 (0%)	0	2/105 (1.9%)	2
Other (Not Including Serious) Adverse Events
	Cognitive Training		Control Training
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	42/108 (38.9%)		54/105 (51.4%)
Gastrointestinal disorders
Nausea	6/108 (5.6%)	6	6/105 (5.7%)	6
Nervous system disorders
Headache	10/108 (9.3%)	11	12/105 (11.4%)	12
Psychiatric disorders
Insomnia	22/108 (20.4%)	35	37/105 (35.2%)	59
Disturbing Dreams	10/108 (9.3%)	10	12/105 (11.4%)	13
Respiratory, thoracic and mediastinal disorders
Shortness of Breath	4/108 (3.7%)	5	7/105 (6.7%)	7
Skin and subcutaneous tissue disorders
Skin Irritation	8/108 (7.4%)	11	13/105 (12.4%)	13
Sweating	5/108 (4.6%)	9	7/105 (6.7%)	7

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.