Comparison of Varenicline and Placebo for Smoking Cessation in Schizophrenia

• Sponsor: University of Maryland, Baltimore (Other)
• Overall Status: Completed
• CT.gov ID: NCT00554840
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 16
• Arms: 2
• Duration (Months): 41

Study Details

Study Description

Brief Summary

The purpose of this proposed pilot study is to examine the use of varenicline in people with schizophrenia to specifically assess tolerability and efficacy for smoking cessation. Specifically, The primary objective of this pilot study is to determine if taking of varenicline along with an individual smoking cessation supportive program is a safe and effective treatment of nicotine addiction in schizophrenic patients. We hypothesize that the varenicline treated patients will achieve higher rates of smoking cessation than those who receive placebo and individual support.

Condition or Disease	Intervention/Treatment	Phase
Cigarette Smoking; Schizophrenia	Drug: varenicline; Drug: placebo	Phase 2

Detailed Description

The primary objective of the data analysis will be to measure the rate of smoking cessation in the two treatment groups. Smoking cessation will be measured weekly through a composite measure of self-reported abstinence, end expired carbon monoxide (CO) of less than C10 ppm and urine cotinine dipstick measure of < 30 ng/ml. The primary endpoint will be point prevalence at 12 weeks. The four week continuous abstinence rate for the last four weeks of the treatment phase will also be evaluated. The point prevalence abstinence rates will also be obtained. The secondary objective is to determine whether smoking cessation is associated with a worsening of cognition and psychiatric symptomology. We hypothesize that subjects who achieve abstinence in the varenicline group will not show worsening on neurocognitive and symptom measures compared to abstinence subjects in the placebo group. Lastly, we will attempt to identify any clinical or topographic markers which predict cessation.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Comparison of Varenicline and Placebo for Smoking Cessation in Schizophrenia
• Study Start Date: Nov 1, 2007
• Actual Primary Completion Date: Dec 1, 2010
• Actual Study Completion Date: Apr 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: varenicline	Drug: varenicline; Subjects will be randomized to receive either active drug or matching placebo capsules using the following titration schedule: 0.5mg for three days, 0.5mg twice daily for the next four days, then 1mg twice daily for the rest of the treatment phase. Subjects will be evaluated weekly for abstinence through self report, end expired CO and urine dipstick for cotinine.; Other Names: chantix, study drug
Placebo Comparator: placebo	Drug: placebo; At the end of Pre-med week 1, subjects will receive study medication with the target quit date being the following week. Subjects will be randomized to receive either active drug or matching placebo capsules using the following titration schedule: 0.5mg for three days, 0.5mg twice daily for the next four days, then 1mg twice daily for the rest of the treatment phase. Subjects will be evaluated weekly for abstinence through self report, end expired CO and urine dipstick for cotinine.; Other Names: sugar pill

Outcome Measures

Primary Outcome Measures

1. Change of ExpiredCO Level From Baseline [Weekly for 12 weeks]

   End expired carbon monoxide (CO) level change from baseline to determine participants' level of smoking reduction by treatment assignment. Larger negative values represent a greater level of smoking reduction.

2. Level of Nicotine Dependence by Treatment Assignment [Weekly for 12 weeks]

   Nicotine dependence was measured using the total score from the Fagerstrom Test for Nicotine Dependence (FTND) assessment. The total score is computed by adding the scores from the five subscales. Total scores range from 1-10, with lower scores representing a smaller degree of nicotine dependence.

Secondary Outcome Measures

1. Brief Psychiatric Rating Scale (BPRS) - Total Score [Baseline (week 0) then again during the Treatment Phase at weeks 1, 2, 4, 8, and 12.]

   The total BPRS score is calculated by adding the scores for subscales #1-#18. Each scale ranges from "1=Not Present" to "7=Very Severe". Total scores range from a minimum score of 18 to a maximum score of 126. A higher total score indicates a more severe psychiatric symptom rating.

2. Brief Psychiatric Rating Scale (BPRS) - Psychosis Score [Baseline (week 0) then again during the Treatment Phase at weeks 1, 2, 4, 8, and 12.]

   The psychosis score is calculated by adding the scores for scales #4 Conceptual Disorganization, #11 Suspiciousness, #12 Hallucinatory Behavior, and #15 Unusual Thought Content. Each scale ranges from "1=Not Present" to "7=Very Severe". The minimum psychosis score is 4 and the maximum psychosis score is 28. A higher score indicates a more severe psychosis rating.

3. Brief Psychiatric Rating Scale (BPRS) - Anxiety/Depression Score [Baseline (week 0) then again during the Treatment Phase at weeks 1, 2, 4, 8, and 12.]

   The anxiety/depression score is calculated by adding the scores for scales #2 Anxiety and #9 Depressive Mood. Each scale ranges from "1=Not Present" to "7=Very Severe". The minimum anxiety/depression score is 2 and the maximum psychosis score is 14. A higher score indicates a more severe anxiety/depression rating.

4. Side Effects [Weekly for 12 weeks]

   Side effects (33 items) were measured using a Side Effects Checklist (SEC). The percentage of participants endorsing each side effect were reported regardless of the severity or relation to study drug.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 64 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age 18-64

• Regular ten cigarette per day smoker for one year

• Nicotine Dependency Score greater than or equal to four

• DSM-IV Diagnosis of Schizophrenia or Schizoaffective disorder

• Psychiatric medication regimen unchanged for at least 90 days

• Psychiatric medication dosage unchanged for at least 30 days

Exclusion Criteria:

• Psychiatric hospitalization in last 6 months

• Meets criteria for current Major Depressive Disorder or has a score of greater than 10 on the Calgary Depression Scale (see withdrawal criteria)

• Suicide or homicide ideation with a plan in the last six months

• Life time history of suicide attempt

• Has had a diagnosis of Schizophrenia or Schizoaffective disorder for less than three years

• Current treatment with Bupropion SR

• DSM-IV diagnosis of alcohol or substance dependence within last 6 months*

• DSM-IV diagnosis of alcohol or substance abuse within three months *

• Pregnancy or lactation in females (+HCG)

• Use of tobacco product other than cigarettes

• Use of nicotine replacements

• Unstable or serious medical condition in last 6 months

• Regular use of cimetidine (OTC or Rx) *Substance abuse/dependency exclusions do not apply to abuse of or dependence on nicotine.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• University of Maryland, Baltimore
• National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Elaine Weiner, M.D., Maryland Psychiatric Research Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: MPRC, Physician, Maryland Psychiatric Research Center, Outpatient Research Program, University of Maryland, Baltimore
• ClinicalTrials.gov Identifier: NCT00554840
• Other Study ID Numbers: HP-00042225
• First Posted: Nov 7, 2007
• Last Update Posted: Mar 18, 2022
• Last Verified: Mar 1, 2022

• Additional relevant MeSH terms: Schizophrenia; Varenicline

Study Results

Participant Flow

Recruitment Details	Stable outpatients who received their regular treatment at the Outpatient Research Program of the MPRC were invited to participate.
Pre-assignment Detail	After the enrollment of 16 participants, a total of 7 participants were withdrawn from the study prior to assignment to a treatment group (n=9). Two subjects met exclusion criteria before any study procedures were started, and 5 subjects were withdrawn during either the "evaluation" or "pre-med" phases of the study.

Arm/Group Title	Varenicline	Placebo
Arm/Group Description	varenicline: Subjects will be randomized to receive either active drug or matching placebo capsules using the following titration schedule: 0.5mg for three days, 0.5mg twice daily for the next four days, then 1mg twice daily for the rest of the treatment phase. Subjects will be evaluated weekly for abstinence through self report, end expired CO and urine dipstick for cotinine.	placebo: At the end of Pre-med week 1, subjects will receive study medication with the target quit date being the following week. Subjects will be randomized to receive either active drug or matching placebo capsules using the following titration schedule: 0.5mg for three days, 0.5mg twice daily for the next four days, then 1mg twice daily for the rest of the treatment phase. Subjects will be evaluated weekly for abstinence through self report, end expired CO and urine dipstick for cotinine.
Period Title: Overall Study
STARTED	4	5
COMPLETED	4	4
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Varenicline	Placebo	Total
Arm/Group Description	varenicline: Subjects will be randomized to receive either active drug or matching placebo capsules using the following titration schedule: 0.5mg for three days, 0.5mg twice daily for the next four days, then 1mg twice daily for the rest of the treatment phase. Subjects will be evaluated weekly for abstinence through self report, end expired CO and urine dipstick for cotinine.	placebo: At the end of Pre-med week 1, subjects will receive study medication with the target quit date being the following week. Subjects will be randomized to receive either active drug or matching placebo capsules using the following titration schedule: 0.5mg for three days, 0.5mg twice daily for the next four days, then 1mg twice daily for the rest of the treatment phase. Subjects will be evaluated weekly for abstinence through self report, end expired CO and urine dipstick for cotinine.	Total of all reporting groups
Overall Participants	4	4	8
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	4 100%	4 100%	8 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46.3 (9.0)	44.3 (5.1)	45.97 (6.87)
Sex: Female, Male (Count of Participants)
Female	1 25%	1 25%	2 25%
Male	3 75%	3 75%	6 75%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	1 25%	1 12.5%
White	3 75%	3 75%	6 75%
More than one race	1 25%	0 0%	1 12.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	4 100%	4 100%	8 100%

Outcome Measures

1. Primary Outcome

Title	Change of ExpiredCO Level From Baseline
Description	End expired carbon monoxide (CO) level change from baseline to determine participants' level of smoking reduction by treatment assignment. Larger negative values represent a greater level of smoking reduction.
Time Frame	Weekly for 12 weeks

Outcome Measure Data

Analysis Population Description

Some ExpiredCO data is missing due to rater error or participant absence from that study visit.

Arm/Group Title	Varenicline	Placebo
Arm/Group Description	Subjects randomized to active treatment (varenicline) will use the following titration schedule: 0.5mg for three days, 0.5mg twice daily for the next four days, then 1mg twice daily for the rest of the treatment phase.	Subjects randomized to matching placebo capsules will use the following titration schedule: 0.5mg for three days, 0.5mg twice daily for the next four days, then 1mg twice daily for the rest of the treatment phase.
Measure Participants	4	4
Treatment Week 1	-2.88 (8.35)	9.5 (6.54)
Treatment Week 2	-17.38 (22.21)	-11.5 (6.94)
Treatment Week 3	-17.13 (23.59)	-5.75 (2.40)
Treatment Week 4	-18.63 (20.77)	2.5 (4.10)
Treatment Week 5	-20.63 (20.27)	-4.5 (4.02)
Treatment Week 6	-20.38 (20.55)	-3.83 (7.25)
Treatment Week 7	-20.13 (20.46)	-2.83 (7.11)
Treatment Week 8	-20.88 (19.28)	-4.83 (8.40)
Treatment Week 9	-20.88 (19.98)	-0.17 (12.55)
Treatment Week 10	-21.13 (19.38)	-2.83 (9.78)
Treatment Week 11	-19.63 (20.72)	8.17 (17.19)
Treatment Week 12	-19.875 (18.98)	-0.75 (6.64)

2. Primary Outcome

Title	Level of Nicotine Dependence by Treatment Assignment
Description	Nicotine dependence was measured using the total score from the Fagerstrom Test for Nicotine Dependence (FTND) assessment. The total score is computed by adding the scores from the five subscales. Total scores range from 1-10, with lower scores representing a smaller degree of nicotine dependence.
Time Frame	Weekly for 12 weeks

Outcome Measure Data

Analysis Population Description

Some FTND data is missing due to rater error or participant absence from that study visit.

Arm/Group Title	Varenicline	Placebo
Arm/Group Description	Subjects randomized to active treatment (varenicline) will use the following titration schedule: 0.5mg for three days, 0.5mg twice daily for the next four days, then 1mg twice daily for the rest of the treatment phase.	Subjects randomized to matching placebo capsules will use the following titration schedule: 0.5mg for three days, 0.5mg twice daily for the next four days, then 1mg twice daily for the rest of the treatment phase.
Measure Participants	4	4
Treatment Week 0	5.88 (1.31)	5.75 (2.10)
Treatment Week 1	4.5 (1.30)	5.25 (2.06)
Treatment Week 2	4.33 (0.58)	4.75 (2.06)
Treatment Week 3	3 (3)	4.5 (1.91)
Treatment Week 4	3 (3)	5 (1.83)
Treatment Week 5	2.75 (2.22)	5.25 (1.71)
Treatment Week 6	4.25 (1.71)	4.33 (1.53)
Treatment Week 7	4.5 (1.73)	4.67 (1.53)
Treatment Week 8	4.75 (1.89)	4 (1.73)
Treatment Week 9	5 (2.16)	3.67 (2.08)
Treatment Week 10	5 (2)	3.67 (2.08)
Treatment Week 11	6 (1)	4.33 (1.53)
Treatment Week 12	3.5 (3.11)	4.25 (1.5)

3. Secondary Outcome

Title	Brief Psychiatric Rating Scale (BPRS) - Total Score
Description	The total BPRS score is calculated by adding the scores for subscales #1-#18. Each scale ranges from "1=Not Present" to "7=Very Severe". Total scores range from a minimum score of 18 to a maximum score of 126. A higher total score indicates a more severe psychiatric symptom rating.
Time Frame	Baseline (week 0) then again during the Treatment Phase at weeks 1, 2, 4, 8, and 12.

Outcome Measure Data

Analysis Population Description

Some BPRS total score data is missing due to rater error or participant absence from that study visit.

Arm/Group Title	Varenicline	Placebo
Arm/Group Description	varenicline: Subjects will be randomized to receive either active drug or matching placebo capsules using the following titration schedule: 0.5mg for three days, 0.5mg twice daily for the next four days, then 1mg twice daily for the rest of the treatment phase. Subjects will be evaluated weekly for abstinence through self report, end expired CO and urine dipstick for cotinine.	placebo: At the end of Pre-med week 1, subjects will receive study medication with the target quit date being the following week. Subjects will be randomized to receive either active drug or matching placebo capsules using the following titration schedule: 0.5mg for three days, 0.5mg twice daily for the next four days, then 1mg twice daily for the rest of the treatment phase. Subjects will be evaluated weekly for abstinence through self report, end expired CO and urine dipstick for cotinine.
Measure Participants	4	4
Baseline	35.75 (6.34)	30.25 (4.11)
Treatment Week 1	33.75 (5.56)	32.75 (6.6)
Treatment Week 2	35.5 (7)	30.25 (4.35)
Treatment Week 4	31.75 (3.4)	30.25 (6.75)
Treatment Week 8	36.25 (4.27)	28 (2.65)
Treatment Week 12	34.75 (3.30)	32 (3.92)

4. Secondary Outcome

Title	Brief Psychiatric Rating Scale (BPRS) - Psychosis Score
Description	The psychosis score is calculated by adding the scores for scales #4 Conceptual Disorganization, #11 Suspiciousness, #12 Hallucinatory Behavior, and #15 Unusual Thought Content. Each scale ranges from "1=Not Present" to "7=Very Severe". The minimum psychosis score is 4 and the maximum psychosis score is 28. A higher score indicates a more severe psychosis rating.
Time Frame	Baseline (week 0) then again during the Treatment Phase at weeks 1, 2, 4, 8, and 12.

Outcome Measure Data

Analysis Population Description

Some BPRS total score data is missing due to rater error or participant absence from that study visit.

Arm/Group Title	Varenicline	Placebo
Arm/Group Description	varenicline: Subjects will be randomized to receive either active drug or matching placebo capsules using the following titration schedule: 0.5mg for three days, 0.5mg twice daily for the next four days, then 1mg twice daily for the rest of the treatment phase. Subjects will be evaluated weekly for abstinence through self report, end expired CO and urine dipstick for cotinine.	placebo: At the end of Pre-med week 1, subjects will receive study medication with the target quit date being the following week. Subjects will be randomized to receive either active drug or matching placebo capsules using the following titration schedule: 0.5mg for three days, 0.5mg twice daily for the next four days, then 1mg twice daily for the rest of the treatment phase. Subjects will be evaluated weekly for abstinence through self report, end expired CO and urine dipstick for cotinine.
Measure Participants	4	4
Baseline	11.25 (2.22)	10 (5.94)
Treatment Week 1	8.5 (3.12)	11.5 (6.03)
Treatment Week 2	9.25 (4.03)	8.5 (4.51)
Treatment Week 4	8.25 (4.03)	8.5 (4.65)
Treatment Week 8	10.75 (3.3)	7.67 (1.53)
Treatment Week 12	8.75 (2.22)	10.5 (3.87)

5. Secondary Outcome

Title	Brief Psychiatric Rating Scale (BPRS) - Anxiety/Depression Score
Description	The anxiety/depression score is calculated by adding the scores for scales #2 Anxiety and #9 Depressive Mood. Each scale ranges from "1=Not Present" to "7=Very Severe". The minimum anxiety/depression score is 2 and the maximum psychosis score is 14. A higher score indicates a more severe anxiety/depression rating.
Time Frame	Baseline (week 0) then again during the Treatment Phase at weeks 1, 2, 4, 8, and 12.

Outcome Measure Data

Analysis Population Description

Some BPRS anxiety/depression score data is missing due to rater error or participant absence from that study visit.

Arm/Group Title	Varenicline	Placebo
Arm/Group Description	varenicline: Subjects will be randomized to receive either active drug or matching placebo capsules using the following titration schedule: 0.5mg for three days, 0.5mg twice daily for the next four days, then 1mg twice daily for the rest of the treatment phase. Subjects will be evaluated weekly for abstinence through self report, end expired CO and urine dipstick for cotinine.	placebo: At the end of Pre-med week 1, subjects will receive study medication with the target quit date being the following week. Subjects will be randomized to receive either active drug or matching placebo capsules using the following titration schedule: 0.5mg for three days, 0.5mg twice daily for the next four days, then 1mg twice daily for the rest of the treatment phase. Subjects will be evaluated weekly for abstinence through self report, end expired CO and urine dipstick for cotinine.
Measure Participants	4	4
Baseline	5.5 (1.3)	6.75 (2.06)
Treatment Week 1	3.25 (0.96)	8 (3.27)
Treatment Week 2	7.25 (1.71)	7.25 (2.99)
Treatment Week 4	6.25 (1.71)	8 (4.32)
Treatment Week 8	7.25 (0.5)	3.37 (2.52)
Treatment Week 12	7 (1.41)	7.5 (2.65)

6. Secondary Outcome

Title	Side Effects
Description	Side effects (33 items) were measured using a Side Effects Checklist (SEC). The percentage of participants endorsing each side effect were reported regardless of the severity or relation to study drug.
Time Frame	Weekly for 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Varenicline	Placebo
Arm/Group Description	Subjects randomized to active treatment (varenicline) will use the following titration schedule: 0.5mg for three days, 0.5mg twice daily for the next four days, then 1mg twice daily for the rest of the treatment phase.	Subjects randomized to matching placebo capsules will use the following titration schedule: 0.5mg for three days, 0.5mg twice daily for the next four days, then 1mg twice daily for the rest of the treatment phase.
Measure Participants	4	4
Abdominal pain	1 25%	4 100%
Anorexia	0 0%	1 25%
Bruising	0 0%	0 0%
Constipation	2 50%	0 0%
Diarrhea	1 25%	0 0%
Dizziness	1 25%	2 50%
Dry mouth	0 0%	2 50%
Enuresis	0 0%	2 50%
Fever	0 0%	0 0%
Headache	1 25%	1 25%
Insomnia	3 75%	1 25%
Malaise	2 50%	1 25%
Mucosal ulceration	0 0%	0 0%
Nausea	3 75%	1 25%
Rash	1 25%	1 25%
Restlessness	0 0%	1 25%
Hypersalivation	3 75%	1 25%
Sedation	2 50%	2 50%
Stiffness	0 0%	1 25%
Sore throat	1 25%	1 25%
Tremor	0 0%	1 25%
Uticaria	1 25%	1 25%
Vomiting	0 0%	1 25%
Weight loss	1 25%	0 0%
Tinnitus	0 0%	0 0%

Adverse Events

Time Frame	Adverse event data was collected for each participant for their entire duration of the study (up to 20 weeks).
Arm/Group Title	Varenicline		Placebo
Arm/Group Description	Subjects randomized to receive active drug (varenicline) will have the following titration schedule: 0.5mg for three days, 0.5mg twice daily for the next four days, then 1mg twice daily for the rest of the treatment phase.		Subjects randomized to matching placebo will have the following titration schedule: 0.5mg for three days, 0.5mg twice daily for the next four days, then 1mg twice daily for the rest of the treatment phase.
All Cause Mortality
	Varenicline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Varenicline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		1/4 (25%)
Psychiatric disorders
Hospitalization	0/4 (0%)	0	1/4 (25%)	1
Other (Not Including Serious) Adverse Events
	Varenicline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/4 (75%)		1/4 (25%)
Ear and labyrinth disorders
Dizziness	1/4 (25%)	1	0/4 (0%)	0
General disorders
Headache	1/4 (25%)	1	0/4 (0%)	0
Dry mouth	0/4 (0%)	0	1/4 (25%)	1
Malaise	1/4 (25%)	3	0/4 (0%)	0
Abdominal pain	1/4 (25%)	1	0/4 (0%)	0
Hepatobiliary disorders
Elevated liver enzymes	1/4 (25%)	1	0/4 (0%)	0
Skin and subcutaneous tissue disorders
Rash	1/4 (25%)	1	1/4 (25%)	1

Limitations/Caveats

Larger studies are needed to confirm these encouraging results.

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.