Trial Outcomes & Findings for Cognitive Remediation With D-Cycloserine (NCT NCT01399866)
NCT ID: NCT01399866
Last Updated: 2018-09-26
Results Overview
Participants assigned to receive D-cycloserine + CET will achieve better maintenance of tobacco abstinence, as assessed with self-report and saliva cotinine measurements, than those who receive placebo + CET at week 6 follow up visits
COMPLETED
PHASE3
150 participants
Up to 6 weeks
2018-09-26
Participant Flow
One hundred fifty participants were enrolled (signed consent), but only 98 were found eligible and started study procedures. Eighty one participants started smoking cessation CBT, and 62 finished and were randomized to receive either D-cycloserine or identical placebo added to exposure treatment to prevent relapse to smoking.
Participants received their choice of nicotine patch or varenicline (0.5 mg per day for 3 days, 0.5 mg bid for 4 days, 1 mg bid for 4 wks) and weekly cognitive behavioral therapy for smoking cessation.
Participant milestones
| Measure |
Placebo
50 mg capsule,single dose, twice, one week apart, by mouth
Placebo
|
D-cycloserine
50 mg capsule,single dose, twice, one week apart, by mouth
D-cycloserine: 2 single weekly doses, 50 mg capsule
|
|---|---|---|
|
Overall Study
STARTED
|
32
|
30
|
|
Overall Study
COMPLETED
|
28
|
28
|
|
Overall Study
NOT COMPLETED
|
4
|
2
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Cognitive Remediation With D-Cycloserine
Baseline characteristics by cohort
| Measure |
Placebo
n=32 Participants
50 mg capsule,single dose, twice, one week apart, by mouth
Placebo
|
D-cycloserine
n=30 Participants
50 mg capsule,single dose, twice, one week apart, by mouth
D-cycloserine: 2 single weekly doses, 50 mg capsule
|
Total
n=62 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
47.1 years
STANDARD_DEVIATION 11.4 • n=5 Participants
|
48.4 years
STANDARD_DEVIATION 12.4 • n=7 Participants
|
47.7 years
STANDARD_DEVIATION 11.8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
19 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
41 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 6 weeksParticipants assigned to receive D-cycloserine + CET will achieve better maintenance of tobacco abstinence, as assessed with self-report and saliva cotinine measurements, than those who receive placebo + CET at week 6 follow up visits
Outcome measures
| Measure |
Placebo
n=32 Participants
50 mg capsule,single dose, twice, one week apart, by mouth
Placebo
|
D-cycloserine
n=30 Participants
50 mg capsule,single dose, twice, one week apart, by mouth
D-cycloserine: 2 single weekly doses, 50 mg capsule
|
|---|---|---|
|
Effect of D-cycloserine + Cue-exposure Treatment on Continuous Abstinence From Tobacco Smoking.
|
9 percentage of participants
|
30 percentage of participants
|
SECONDARY outcome
Timeframe: 6 weeksRecently abstinent smokers assigned to receive D-cycloserine + CET will have less physiologic (skin conductance) reactivity to smoking cues at the Post-Extinction Assessment than those who receive placebo + CET. Subjects were presented with 2 blocks of audio recordings, one smoking-related script and one neutral script unrelated to smoking. Assessment of skin conductance was made after each audio recording was presented. The skin conductance mean was obtained for each script (smoking vs neutral). Differences in responsivity (skin conductance) to smoking cues (smoking script) was compared between subjects who received D-cycloserine + CET and subjects who received placebo + CET.
Outcome measures
| Measure |
Placebo
n=32 Participants
50 mg capsule,single dose, twice, one week apart, by mouth
Placebo
|
D-cycloserine
n=30 Participants
50 mg capsule,single dose, twice, one week apart, by mouth
D-cycloserine: 2 single weekly doses, 50 mg capsule
|
|---|---|---|
|
Effect of D-cycloserine + Cue-exposure Treatment on Skin Conductance
|
0.14 change in microSiemens
Standard Deviation 0.46
|
0.18 change in microSiemens
Standard Deviation 0.31
|
SECONDARY outcome
Timeframe: 6 weeksRecently abstinent smokers assigned to receive D-cycloserine + CET will have less physiologic (heart rate) reactivity to smoking cues at the Post-Extinction Assessment than those who receive placebo + CET. Subjects were presented with 2 blocks of audio recordings, one smoking-related script and one neutral script unrelated to smoking. Heart rate measurement was obtained after each audio recording was presented. The heart rate mean was obtained for each script (smoking vs neutral). Differences in responsivity (heart rate) to smoking cues (smoking script) was compared between subjects who received D-cycloserine + CET and subjects who received placebo + CET.
Outcome measures
| Measure |
Placebo
n=32 Participants
50 mg capsule,single dose, twice, one week apart, by mouth
Placebo
|
D-cycloserine
n=30 Participants
50 mg capsule,single dose, twice, one week apart, by mouth
D-cycloserine: 2 single weekly doses, 50 mg capsule
|
|---|---|---|
|
Effect of D-cycloserine + Cue-exposure Treatment on Heart Rate
|
-0.13 change in beats per minute
Standard Deviation 2.64
|
0.98 change in beats per minute
Standard Deviation 2.34
|
SECONDARY outcome
Timeframe: 6 weeksRecently abstinent smokers assigned to receive D-cycloserine + CET will have less physiologic (electromyogram) reactivity to smoking cues at the Post-Extinction Assessment than those who receive placebo + CET. Subjects were presented with 2 blocks of audio recordings, one smoking-related script and one neutral script unrelated to smoking. Electromyogram of the corrugator (EMGc)measurement was obtained after each audio recording was presented. The EMGc mean was obtained for each script (smoking vs neutral). Differences in responsivity (EMGc) to smoking cues (smoking script) was compared between subjects who received D-cycloserine + CET and subjects who received placebo + CET.
Outcome measures
| Measure |
Placebo
n=32 Participants
50 mg capsule,single dose, twice, one week apart, by mouth
Placebo
|
D-cycloserine
n=30 Participants
50 mg capsule,single dose, twice, one week apart, by mouth
D-cycloserine: 2 single weekly doses, 50 mg capsule
|
|---|---|---|
|
Effect of D-cycloserine + Cue-exposure Treatment on Electromyogram
|
0.25 change in micro volts
Standard Deviation 1.02
|
0.46 change in micro volts
Standard Deviation 1.52
|
SECONDARY outcome
Timeframe: 6 weeksRecently abstinent smokers assigned to receive D-cycloserine + CET will have less craving at the Post-Extinction Assessment than those who receive placebo + CET The scale used to measure craving was a Visual Analogue Scale 0 (no desire at all) - 7 (unable to resist) Subjects were presented with 2 blocks of audio recordings, one smoking-related script and one neutral script unrelated to smoking. Craving level was obtained after each audio recording was presented. The craving mean was obtained for each script (smoking vs neutral). Differences in craving level response to smoking cues (smoking script) was compared between subjects who received D-cycloserine + CET and subjects who received placebo + CET.
Outcome measures
| Measure |
Placebo
n=32 Participants
50 mg capsule,single dose, twice, one week apart, by mouth
Placebo
|
D-cycloserine
n=30 Participants
50 mg capsule,single dose, twice, one week apart, by mouth
D-cycloserine: 2 single weekly doses, 50 mg capsule
|
|---|---|---|
|
Effect of D-cycloserine + Cue-exposure Treatment on Craving
|
2.28 change in units on a scale
Standard Deviation 2.30
|
1.44 change in units on a scale
Standard Deviation 1.87
|
SECONDARY outcome
Timeframe: Baseline and week 6Recently abstinent smokers assigned to receive D-cycloserine + CET will have less attentional bias (Smoking Stroop task) toward smoking cues at the Post-Extinction Assessment than those who receive placebo + CET The Emotional Stroop uses smoking-related words and neutral words to measure attentional bias toward smoking related cues. Attentional bias is a central feature of many cognitive theories of addiction and can be measured with an emotional analog of the Stroop task. In this task, participants name the colors in which words are printed, and the words vary in their relevance to smoking. Extensive research has shown that patients are often slower to name the color of a word associated with concerns relevant to their clinical condition due to distraction by the meaning of the word(Williams, Mathews et al. 1996). The Stroop interference Score is obtained by subtracting Reaction Time (RT) to smoking minus the Reaction Time to neutral
Outcome measures
| Measure |
Placebo
n=32 Participants
50 mg capsule,single dose, twice, one week apart, by mouth
Placebo
|
D-cycloserine
n=30 Participants
50 mg capsule,single dose, twice, one week apart, by mouth
D-cycloserine: 2 single weekly doses, 50 mg capsule
|
|---|---|---|
|
Effect of D-cycloserine + Cue-exposure Treatment on Attentional Bias Toward Smoking Cuesmeasured With the Emotional Stroop Task
|
35.27 Stroop interference Score
Standard Deviation 74.93
|
50.30 Stroop interference Score
Standard Deviation 74.85
|
Adverse Events
Placebo
D-cycloserine
Serious adverse events
| Measure |
Placebo
n=32 participants at risk
50 mg capsule,single dose, twice, one week apart, by mouth
Placebo
|
D-cycloserine
n=30 participants at risk
50 mg capsule,single dose, twice, one week apart, by mouth
D-cycloserine: 2 single weekly doses, 50 mg capsule
|
|---|---|---|
|
Musculoskeletal and connective tissue disorders
compression fracture
|
3.1%
1/32
|
0.00%
0/30
|
Other adverse events
| Measure |
Placebo
n=32 participants at risk
50 mg capsule,single dose, twice, one week apart, by mouth
Placebo
|
D-cycloserine
n=30 participants at risk
50 mg capsule,single dose, twice, one week apart, by mouth
D-cycloserine: 2 single weekly doses, 50 mg capsule
|
|---|---|---|
|
General disorders
Anorexia
|
6.2%
2/32
|
13.3%
4/30
|
|
General disorders
Blurred vision
|
9.4%
3/32
|
10.0%
3/30
|
|
Gastrointestinal disorders
Constipation
|
18.8%
6/32
|
20.0%
6/30
|
|
Psychiatric disorders
Depressen mood
|
28.1%
9/32
|
30.0%
9/30
|
|
Gastrointestinal disorders
Diarrhea
|
28.1%
9/32
|
6.7%
2/30
|
|
General disorders
Dizziness
|
9.4%
3/32
|
13.3%
4/30
|
|
General disorders
Dry mouth
|
28.1%
9/32
|
23.3%
7/30
|
|
General disorders
Enuresis
|
9.4%
3/32
|
6.7%
2/30
|
|
General disorders
Fever
|
6.2%
2/32
|
3.3%
1/30
|
|
General disorders
Headache
|
12.5%
4/32
|
10.0%
3/30
|
|
General disorders
Hypersalivation
|
6.2%
2/32
|
6.7%
2/30
|
|
General disorders
Insomnia
|
25.0%
8/32
|
23.3%
7/30
|
|
Psychiatric disorders
Irritability
|
34.4%
11/32
|
30.0%
9/30
|
|
General disorders
Malaise
|
21.9%
7/32
|
13.3%
4/30
|
|
Gastrointestinal disorders
Nausea
|
15.6%
5/32
|
6.7%
2/30
|
|
Skin and subcutaneous tissue disorders
Skin rash
|
15.6%
5/32
|
13.3%
4/30
|
|
Psychiatric disorders
Restlessness
|
6.2%
2/32
|
23.3%
7/30
|
|
General disorders
Drowsiness
|
18.8%
6/32
|
16.7%
5/30
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
12.5%
4/32
|
20.0%
6/30
|
|
General disorders
Stiffness
|
9.4%
3/32
|
13.3%
4/30
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
6.2%
2/32
|
16.7%
5/30
|
|
Gastrointestinal disorders
Vomiting
|
6.2%
2/32
|
6.7%
2/30
|
|
General disorders
Other
|
43.8%
14/32
|
50.0%
15/30
|
Additional Information
A. Eden Evins, MD, MPH. Director of the MGH-Harvard Center for Addiction Medicine
Massachusetts General Hospital - Harvard Medical School
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place