Trial Outcomes & Findings for Nicotinic Modulation of the Default Network (NCT NCT01223404)

Results Overview

average reaction time on cognitive task performed in the MR scanner

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

21 participants

Primary outcome timeframe

1 day

Results posted on

2019-08-19

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo, Nicotine, Mecamylamine First session: Placebo patch and placebo capsule (filler: methylcellulose) Second session: Nicotine patch and Placebo capsule (filler: methylcellulose) Third session: Placebo patch and Mecamylamine capsule	Nicotine, Placebo, Mecamylamine First session: Nicotine patch and placebo capsule (filler: methylcellulose) Second session: Placebo patch and Placebo capsule (filler: methylcellulose) Third session: Placebo patch and Mecamylamine capsule	Placebo, Mecamylamine, Nicotine First session: Placebo patch and Placebo capsule (filler: methylcellulose) Second session: Placebo patch and Mecamylamine capsule Third session: Nicotine patch and Placebo capsule (filler: methylcellulose)	Nicotine, Mecamylamine, Placebo First session: Nicotine patch and placebo capsule (filler: methylcellulose) Second session: Placebo patch and Mecamylamine capsule Third session: Placebo patch and Placebo capsule (filler: methylcellulose)	Mecamylamine, Placebo, Nicotine First session: Placebo patch and Mecamylamine capsule Second session: Placebo patch and Placebo capsule (filler: methylcellulose) Third session: Nicotine patch and Placebo capsule (filler: methylcellulose)	Mecamylamine, Nicotine, Placebo First session: Placebo patch and Mecamylamine capsule Second session: Nicotine patch and Placebo capsule (filler: methylcellulose) Third session: Placebo patch and Placebo capsule (filler: methylcellulose)
First Intervention (1 Day) STARTED	4	3	4	5	2	3
First Intervention (1 Day) COMPLETED	4	3	4	4	2	3
First Intervention (1 Day) NOT COMPLETED	0	0	0	1	0	0
Second Intervention (1 Day) STARTED	4	3	4	4	2	3
Second Intervention (1 Day) COMPLETED	3	3	4	4	2	3
Second Intervention (1 Day) NOT COMPLETED	1	0	0	0	0	0
Third Intervention (1 Day) STARTED	3	3	4	4	2	3
Third Intervention (1 Day) COMPLETED	3	3	4	3	2	3
Third Intervention (1 Day) NOT COMPLETED	0	0	0	1	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo, Nicotine, Mecamylamine First session: Placebo patch and placebo capsule (filler: methylcellulose) Second session: Nicotine patch and Placebo capsule (filler: methylcellulose) Third session: Placebo patch and Mecamylamine capsule	Nicotine, Mecamylamine, Placebo First session: Nicotine patch and placebo capsule (filler: methylcellulose) Second session: Placebo patch and Mecamylamine capsule Third session: Placebo patch and Placebo capsule (filler: methylcellulose)
First Intervention (1 Day) Adverse Event	0	1
Second Intervention (1 Day) Adverse Event	1	0
Third Intervention (1 Day) Non-compliance (slept)	0	1

Baseline Characteristics

Nicotinic Modulation of the Default Network

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Study Participants n=21 Participants Participants in each of the six arms received all three interventions (placebo, nicotine, mecamylamine).
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	21 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	13 Participants n=5 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	21 participants n=5 Participants

PRIMARY outcome

Timeframe: 1 day

Population: 18 healthy male and female adult non-smokers. Only study completers are included, due to the within-subject design.

average reaction time on cognitive task performed in the MR scanner

Outcome measures

Outcome measures
Measure	Intervention: Placebo n=18 Participants A placebo patch and a placebo capsule are administered.	Intervention: Nicotine n=18 Participants A nicotine patch and a placebo capsule is administered.	Intervention: Mecamylamine n=18 Participants A placebo patch and a mecamylamine capsule are administered.
Reaction Time Attention task reaction time	512 ms Interval 485.0 to 539.0	492 ms Interval 464.0 to 520.0	524 ms Interval 489.0 to 559.0
Reaction Time Working memory task reaction time	541 ms Interval 516.0 to 566.0	533 ms Interval 508.0 to 558.0	573 ms Interval 537.0 to 609.0

PRIMARY outcome

Timeframe: 1 day

Population: Healthy adult non-smokers (only study completers).

Signal detection on cognitive tasks performed in the MR scanner. For the attention task, this represents the percentage of trials in which the participant responded when a signal was presented. In the working memory task (N-back task), this represents the percentage of all target sequences to which the participant responded.

Outcome measures

Outcome measures
Measure	Intervention: Placebo n=18 Participants A placebo patch and a placebo capsule are administered.	Intervention: Nicotine n=18 Participants A nicotine patch and a placebo capsule is administered.	Intervention: Mecamylamine n=18 Participants A placebo patch and a mecamylamine capsule are administered.
Signal Detection Performance Attention task correct identifications	86.4 percentage of all targets Interval 81.4 to 91.4	93.8 percentage of all targets Interval 90.1 to 97.5	85.2 percentage of all targets Interval 79.7 to 90.7
Signal Detection Performance Working memory task correct detections	89.6 percentage of all targets Interval 88.4 to 90.8	95.5 percentage of all targets Interval 94.9 to 96.1	88.6 percentage of all targets Interval 87.9 to 89.3

PRIMARY outcome

Timeframe: 1 day

Population: Healthy non-smokers (only study completers).

Cognitive task-induced default network deactivation, measured by functional Magnetic Resonance Imaging. The default network was probed by five pre-defined ROIs per hemisphere. Task-induced deactivation was averaged across all ROIs.

Outcome measures

Outcome measures
Measure	Intervention: Placebo n=18 Participants A placebo patch and a placebo capsule are administered.	Intervention: Nicotine n=18 Participants A nicotine patch and a placebo capsule is administered.	Intervention: Mecamylamine n=18 Participants A placebo patch and a mecamylamine capsule are administered.
Default Network Activity	-0.29 percentage of task-induced signal change Interval -0.41 to -0.17	-0.24 percentage of task-induced signal change Interval -0.39 to -0.09	-0.21 percentage of task-induced signal change Interval -0.33 to -0.09

SECONDARY outcome

Timeframe: 1 day

Population: Healthy non-smokers (only study completers).

End-of-session subjective state is measured by the Profile of Mood States (POMS). We utilize "Total Mood Disturbance" (TMD) as a summary measure, derived by adding the total scores on the five negative mood scales (tension, depression, anger, fatigue, confusion) and subtracting the score on the one positive mood scale (vigor). The theoretical range of the TMD scale is -32 to 228, with negative values indicating less mood disturbance, i.e., a more positive emotional state.

Outcome measures

Outcome measures
Measure	Intervention: Placebo n=18 Participants A placebo patch and a placebo capsule are administered.	Intervention: Nicotine n=18 Participants A nicotine patch and a placebo capsule is administered.	Intervention: Mecamylamine n=18 Participants A placebo patch and a mecamylamine capsule are administered.
Subjective State	-6.7 units on a scale Interval -12.3 to -1.1	-9.9 units on a scale Interval -15.4 to -4.4	-5.8 units on a scale Interval -12.0 to 0.4

SECONDARY outcome

Timeframe: Bi-hourly: prior to patch application, 2 hours, 4 hours, and 6 hours after, and after the MRI scan (~8 hours after patch application)

Population: Healthy non-smokers

Systolic blood pressure (mmHg)

Outcome measures

Outcome measures
Measure	Intervention: Placebo n=18 Participants A placebo patch and a placebo capsule are administered.	Intervention: Nicotine n=18 Participants A nicotine patch and a placebo capsule is administered.	Intervention: Mecamylamine n=18 Participants A placebo patch and a mecamylamine capsule are administered.
Systolic Blood Pressure 2 hours post patch	116.1 mmHG Standard Deviation 11.9	114.3 mmHG Standard Deviation 10.7	112.3 mmHG Standard Deviation 8.6
Systolic Blood Pressure Pre-patch	120.2 mmHG Standard Deviation 11.4	120.9 mmHG Standard Deviation 16.7	119.3 mmHG Standard Deviation 14.8
Systolic Blood Pressure 4 hours post patch	120.1 mmHG Standard Deviation 16.7	119.1 mmHG Standard Deviation 9.9	114.4 mmHG Standard Deviation 11.4
Systolic Blood Pressure 6 hours post patch	120.3 mmHG Standard Deviation 12.9	122.7 mmHG Standard Deviation 12.7	118.2 mmHG Standard Deviation 14.1
Systolic Blood Pressure Post-scan	129.7 mmHG Standard Deviation 16.1	127.4 mmHG Standard Deviation 9.8	121.5 mmHG Standard Deviation 13.8

SECONDARY outcome

Timeframe: Bi-hourly: prior to patch application, 2 hours, 4 hours, and 6 hours after, and after the MRI scan (~8 hours after patch application).

Population: Healthy non-smokers (only study completers).

Diastolic blood pressure in mmHg.

Outcome measures

Outcome measures
Measure	Intervention: Placebo n=18 Participants A placebo patch and a placebo capsule are administered.	Intervention: Nicotine n=18 Participants A nicotine patch and a placebo capsule is administered.	Intervention: Mecamylamine n=18 Participants A placebo patch and a mecamylamine capsule are administered.
Diastolic Blood Pressure Pre-patch	74.4 mmHG Standard Deviation 8.0	71.6 mmHG Standard Deviation 10.0	73.4 mmHG Standard Deviation 10.1
Diastolic Blood Pressure 2 hours post patch	73.4 mmHG Standard Deviation 10.0	71.9 mmHG Standard Deviation 9.9	73.2 mmHG Standard Deviation 9.7
Diastolic Blood Pressure 4 hours post patch	73.7 mmHG Standard Deviation 9.7	71.1 mmHG Standard Deviation 7.9	72.4 mmHG Standard Deviation 6.9
Diastolic Blood Pressure 6 hours post patch	75.8 mmHG Standard Deviation 6.6	75.3 mmHG Standard Deviation 5.8	75.2 mmHG Standard Deviation 8.1
Diastolic Blood Pressure Post-scan	81.3 mmHG Standard Deviation 5.4	81.1 mmHG Standard Deviation 5.7	79.6 mmHG Standard Deviation 9.4

Adverse Events

Intervention: Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Intervention: Nicotine

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Intervention: Mecamylamine

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Intervention: Placebo n=20 participants at risk Participants receive a placebo patch and a placebo capsule.	Intervention: Nicotine n=21 participants at risk Participants receive a nicotine patch and a placebo capsule.	Intervention: Mecamylamine n=19 participants at risk Participants receive a placebo patch and a mecamylamine capsule.
Gastrointestinal disorders Vomiting	0.00% 0/20 • 1 day (on each of separate 3 test days)	9.5% 2/21 • Number of events 2 • 1 day (on each of separate 3 test days)	0.00% 0/19 • 1 day (on each of separate 3 test days)

Additional Information

Dr. Britta Hahn

University of Maryland School of Medicine

Phone: 4104026112

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place