Trial Outcomes & Findings for Nicotinic Treatment of Post-Chemotherapy Subjective Cognitive Impairment: A Pilot Study (NCT NCT02312934)
NCT ID: NCT02312934
Last Updated: 2020-01-21
Results Overview
The Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) scale will be used to monitor change in CRCI subjective complaints. This instrument has been used to monitor change in CRCI subjective complaints in previous studies and demonstrates good internal consistency, test-retest reliability, and discriminant and convergent validity. Specifically, the PCI subscale was used as the primary outcome measure. The FACT-Cog PCI consists of 20 items and has a minimum score of 0 and total possible score of 72. Higher scores indicate better cognitive functioning. The PCI evaluates memory, concentration, mental acuity, verbal fluency, functional interference, and multitasking ability. Visit 3 is the 3-week visit, Visit 4 is the 6-week visit, and Visit 5 is the 8-week visit. Change scores were calculated as follow
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
22 participants
Primary outcome timeframe
Baseline to 8-Weeks
Results posted on
2020-01-21
Participant Flow
Participants were recruited through Vanderbilt University-affiliated clinics and the greater Nashville, TN community.
Of the 106 people pre-screened for the study, 37 attended the initial screening visit. Twenty-two participants met entry criteria and were randomized. Participants that were not randomized were excluded from the study because they did not meet inclusion/exclusion criteria.
Participant milestones
| Measure |
Transdermal Nicotine
Nicotine will be delivered by a transdermal patch delivery system for topical application. Each patch will contain approximately 1.75mg nicotine/cm2, and releases 7, and 14mg of nicotine, respectively, over 24 hours. Patches will be applied for 16 hours per day. Participants will be titrated over the course of the 6-week treatment period in order to avoid initial side effects as follows:
Week 1: ½ 7 mg patch per day, Week 2: 7 mg patch per day, Weeks 3-4: ¾ 14 mg patch per day, Weeks 5-6: 14 mg per day, Weeks 7-8: Treatment withdrawal
Transdermal nicotine: Nicotine patches are currently FDA approved for smoking cessation. Nicotine has effects that have been well studied for many years. Studies have shown that nicotine by itself does not appear by itself to be cancer causing. The use of the nicotine patch is not expected to increase risk of breast cancer recurrence.
|
Placebo
Matching transdermal placebo patches will be used. Participants will follow the same titration schedule as the transdermal nicotine arm.
Week 1: ½ 7 mg patch per day, Week 2: 7 mg patch per day, Weeks 3-4: ¾ 14 mg patch per day, Weeks 5-6: 14 mg per day, Weeks 7-8: Treatment withdrawal
Placebo Transdermal Patch
|
|---|---|---|
|
Overall Study
STARTED
|
11
|
11
|
|
Overall Study
COMPLETED
|
9
|
11
|
|
Overall Study
NOT COMPLETED
|
2
|
0
|
Reasons for withdrawal
| Measure |
Transdermal Nicotine
Nicotine will be delivered by a transdermal patch delivery system for topical application. Each patch will contain approximately 1.75mg nicotine/cm2, and releases 7, and 14mg of nicotine, respectively, over 24 hours. Patches will be applied for 16 hours per day. Participants will be titrated over the course of the 6-week treatment period in order to avoid initial side effects as follows:
Week 1: ½ 7 mg patch per day, Week 2: 7 mg patch per day, Weeks 3-4: ¾ 14 mg patch per day, Weeks 5-6: 14 mg per day, Weeks 7-8: Treatment withdrawal
Transdermal nicotine: Nicotine patches are currently FDA approved for smoking cessation. Nicotine has effects that have been well studied for many years. Studies have shown that nicotine by itself does not appear by itself to be cancer causing. The use of the nicotine patch is not expected to increase risk of breast cancer recurrence.
|
Placebo
Matching transdermal placebo patches will be used. Participants will follow the same titration schedule as the transdermal nicotine arm.
Week 1: ½ 7 mg patch per day, Week 2: 7 mg patch per day, Weeks 3-4: ¾ 14 mg patch per day, Weeks 5-6: 14 mg per day, Weeks 7-8: Treatment withdrawal
Placebo Transdermal Patch
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
Physician Decision
|
1
|
0
|
Baseline Characteristics
Nicotinic Treatment of Post-Chemotherapy Subjective Cognitive Impairment: A Pilot Study
Baseline characteristics by cohort
| Measure |
Transdermal Nicotine
n=11 Participants
Nicotine will be delivered by a transdermal patch delivery system for topical application. Each patch will contain approximately 1.75mg nicotine/cm2, and releases 7, and 14mg of nicotine, respectively, over 24 hours. Patches will be applied for 16 hours per day. Participants will be titrated over the course of the 6-week treatment period in order to avoid initial side effects as follows:
Week 1: ½ 7 mg patch per day, Week 2: 7 mg patch per day, Weeks 3-4: ¾ 14 mg patch per day, Weeks 5-6: 14 mg per day, Weeks 7-8: Treatment withdrawal
Transdermal nicotine: Nicotine patches are currently FDA approved for smoking cessation. Nicotine has effects that have been well studied for many years. Studies have shown that nicotine by itself does not appear by itself to be cancer causing. The use of the nicotine patch is not expected to increase risk of breast cancer recurrence.
|
Placebo
n=11 Participants
Matching transdermal placebo patches will be used. Participants will follow the same titration schedule as the transdermal nicotine arm.
Week 1: ½ 7 mg patch per day, Week 2: 7 mg patch per day, Weeks 3-4: ¾ 14 mg patch per day, Weeks 5-6: 14 mg per day, Weeks 7-8: Treatment withdrawal
Placebo Transdermal Patch
|
Total
n=22 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
9 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Age, Continuous
|
56.00 Years
STANDARD_DEVIATION 11.58 • n=5 Participants
|
52.55 Years
STANDARD_DEVIATION 7.66 • n=7 Participants
|
54.27 Years
STANDARD_DEVIATION 9.74 • n=5 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
11 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
10 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
11 participants
n=5 Participants
|
11 participants
n=7 Participants
|
25 participants
n=5 Participants
|
|
Cancer Type
Breast Cancer
|
8 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Cancer Type
Non-Hodgekin's Lymphoma
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Cancer Type
Ovarian Cancer
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Cancer Type
Colon Cancer
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Cancer Stage
Stage I
|
3 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Cancer Stage
Stage II
|
3 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Cancer Stage
Stage III
|
4 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Cancer Stage
Stage IV
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Cancer Treatment Received
Chemotherapy
|
11 participants
n=5 Participants
|
11 participants
n=7 Participants
|
22 participants
n=5 Participants
|
|
Cancer Treatment Received
Surgery
|
10 participants
n=5 Participants
|
11 participants
n=7 Participants
|
21 participants
n=5 Participants
|
|
Cancer Treatment Received
Radiation
|
5 participants
n=5 Participants
|
7 participants
n=7 Participants
|
12 participants
n=5 Participants
|
|
Current Endocrine Therapy
Yes
|
6 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Current Endocrine Therapy
No
|
5 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Post-Menopausal Status
Pre-Menopausal
|
5 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Post-Menopausal Status
Post-Menopausal
|
6 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to 8-WeeksThe Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) scale will be used to monitor change in CRCI subjective complaints. This instrument has been used to monitor change in CRCI subjective complaints in previous studies and demonstrates good internal consistency, test-retest reliability, and discriminant and convergent validity. Specifically, the PCI subscale was used as the primary outcome measure. The FACT-Cog PCI consists of 20 items and has a minimum score of 0 and total possible score of 72. Higher scores indicate better cognitive functioning. The PCI evaluates memory, concentration, mental acuity, verbal fluency, functional interference, and multitasking ability. Visit 3 is the 3-week visit, Visit 4 is the 6-week visit, and Visit 5 is the 8-week visit. Change scores were calculated as follow
Outcome measures
| Measure |
Transdermal Nicotine
n=11 Participants
Nicotine will be delivered by a transdermal patch delivery system for topical application. Each patch will contain approximately 1.75mg nicotine/cm2, and releases 7, and 14mg of nicotine, respectively, over 24 hours. Patches will be applied for 16 hours per day. Participants will be titrated over the course of the 6-week treatment period in order to avoid initial side effects as follows:
Week 1: ½ 7 mg patch per day, Week 2: 7 mg patch per day, Weeks 3-4: ¾ 14 mg patch per day, Weeks 5-6: 14 mg per day, Weeks 7-8: Treatment withdrawal
Transdermal nicotine: Nicotine patches are currently FDA approved for smoking cessation. Nicotine has effects that have been well studied for many years. Studies have shown that nicotine by itself does not appear by itself to be cancer causing. The use of the nicotine patch is not expected to increase risk of breast cancer recurrence.
|
Placebo
n=11 Participants
Matching transdermal placebo patches will be used. Participants will follow the same titration schedule as the transdermal nicotine arm.
Week 1: ½ 7 mg patch per day, Week 2: 7 mg patch per day, Weeks 3-4: ¾ 14 mg patch per day, Weeks 5-6: 14 mg per day, Weeks 7-8: Treatment withdrawal
Placebo Transdermal Patch
|
|---|---|---|
|
Change in the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) PCI Scale
Visit 3 PCI Change from Baseline Score (3-Weeks)
|
7.00 units on a scale
Standard Deviation 12.01
|
11.55 units on a scale
Standard Deviation 9.59
|
|
Change in the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) PCI Scale
Visit 4 PCI Change from Baseline Score (6-Weeks)
|
16.80 units on a scale
Standard Deviation 15.47
|
16.64 units on a scale
Standard Deviation 7.58
|
|
Change in the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) PCI Scale
Visit 5 PCI Change from Baseline Score (8-Weeks)
|
11.20 units on a scale
Standard Deviation 14.40
|
16.55 units on a scale
Standard Deviation 10.40
|
SECONDARY outcome
Timeframe: Baseline to 8 WeeksThe secondary outcome measure was the computerized Conners Continuous Performance Test (CPT), which measures sustained attention and vigilance. Participants see a series of letters appearing one at a time on a computer screen and they press a button for every letter that appears on the screen, except for "X". Lower scores indicate better performance. Scores on the CPT are calculated using the each participant's performance on the task (defined as reaction time (in ms) standard error/interstimulus interval). Change scores from baseline are then calculated. A decrease in CPT score = improvement. \*This is not a clinical measure. This is a research measure of reaction time variability and therefore there is no clinical interpretation and no defined score range.\*
Outcome measures
| Measure |
Transdermal Nicotine
n=11 Participants
Nicotine will be delivered by a transdermal patch delivery system for topical application. Each patch will contain approximately 1.75mg nicotine/cm2, and releases 7, and 14mg of nicotine, respectively, over 24 hours. Patches will be applied for 16 hours per day. Participants will be titrated over the course of the 6-week treatment period in order to avoid initial side effects as follows:
Week 1: ½ 7 mg patch per day, Week 2: 7 mg patch per day, Weeks 3-4: ¾ 14 mg patch per day, Weeks 5-6: 14 mg per day, Weeks 7-8: Treatment withdrawal
Transdermal nicotine: Nicotine patches are currently FDA approved for smoking cessation. Nicotine has effects that have been well studied for many years. Studies have shown that nicotine by itself does not appear by itself to be cancer causing. The use of the nicotine patch is not expected to increase risk of breast cancer recurrence.
|
Placebo
n=11 Participants
Matching transdermal placebo patches will be used. Participants will follow the same titration schedule as the transdermal nicotine arm.
Week 1: ½ 7 mg patch per day, Week 2: 7 mg patch per day, Weeks 3-4: ¾ 14 mg patch per day, Weeks 5-6: 14 mg per day, Weeks 7-8: Treatment withdrawal
Placebo Transdermal Patch
|
|---|---|---|
|
Conners Continuous Performance Test
Visit 3 CPT Change from Baseline Score (3-Weeks)
|
0.0127 ms
Standard Deviation 0.11705
|
-0.0318 ms
Standard Deviation 0.1256
|
|
Conners Continuous Performance Test
Visit 4 CPT Change from Baseline Score (6-Weeks)
|
0.01 ms
Standard Deviation 0.17205
|
-0.0355 ms
Standard Deviation 0.12242
|
|
Conners Continuous Performance Test
Visit 5 CPT Change from Baseline Score (8-Weeks)
|
-0.0185 ms
Standard Deviation 0.19357
|
-0.0236 ms
Standard Deviation 0.14009
|
Adverse Events
Transdermal Nicotine
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Transdermal Nicotine
n=11 participants at risk
Nicotine will be delivered by a transdermal patch delivery system for topical application. Each patch will contain approximately 1.75mg nicotine/cm2, and releases 7, and 14mg of nicotine, respectively, over 24 hours. Patches will be applied for 16 hours per day. Participants will be titrated over the course of the 6-week treatment period in order to avoid initial side effects as follows:
Week 1: ½ 7 mg patch per day, Week 2: 7 mg patch per day, Weeks 3-4: ¾ 14 mg patch per day, Weeks 5-6: 14 mg per day, Weeks 7-8: Treatment withdrawal
Transdermal nicotine: Nicotine patches are currently FDA approved for smoking cessation. Nicotine has effects that have been well studied for many years. Studies have shown that nicotine by itself does not appear by itself to be cancer causing. The use of the nicotine patch is not expected to increase risk of breast cancer recurrence.
|
Placebo
n=11 participants at risk
Matching transdermal placebo patches will be used. Participants will follow the same titration schedule as the transdermal nicotine arm.
Week 1: ½ 7 mg patch per day, Week 2: 7 mg patch per day, Weeks 3-4: ¾ 14 mg patch per day, Weeks 5-6: 14 mg per day, Weeks 7-8: Treatment withdrawal
Placebo Transdermal Patch
|
|---|---|---|
|
Skin and subcutaneous tissue disorders
Skin Irritation
|
54.5%
6/11 • Number of events 6 • 8-Weeks
Adverse events were recorded and categorized by body system, event type, attribution, frequency, severity, and course. AEs were assessed across all double-blind study visits and categorized according to body system for all participants who received at least one dose of patches (nicotine n = 12, placebo n = 13).
|
18.2%
2/11 • Number of events 2 • 8-Weeks
Adverse events were recorded and categorized by body system, event type, attribution, frequency, severity, and course. AEs were assessed across all double-blind study visits and categorized according to body system for all participants who received at least one dose of patches (nicotine n = 12, placebo n = 13).
|
|
Gastrointestinal disorders
Gastrointestinal
|
27.3%
3/11 • Number of events 3 • 8-Weeks
Adverse events were recorded and categorized by body system, event type, attribution, frequency, severity, and course. AEs were assessed across all double-blind study visits and categorized according to body system for all participants who received at least one dose of patches (nicotine n = 12, placebo n = 13).
|
27.3%
3/11 • Number of events 3 • 8-Weeks
Adverse events were recorded and categorized by body system, event type, attribution, frequency, severity, and course. AEs were assessed across all double-blind study visits and categorized according to body system for all participants who received at least one dose of patches (nicotine n = 12, placebo n = 13).
|
|
General disorders
Neurologic
|
18.2%
2/11 • Number of events 2 • 8-Weeks
Adverse events were recorded and categorized by body system, event type, attribution, frequency, severity, and course. AEs were assessed across all double-blind study visits and categorized according to body system for all participants who received at least one dose of patches (nicotine n = 12, placebo n = 13).
|
18.2%
2/11 • Number of events 2 • 8-Weeks
Adverse events were recorded and categorized by body system, event type, attribution, frequency, severity, and course. AEs were assessed across all double-blind study visits and categorized according to body system for all participants who received at least one dose of patches (nicotine n = 12, placebo n = 13).
|
|
General disorders
Mood
|
0.00%
0/11 • 8-Weeks
Adverse events were recorded and categorized by body system, event type, attribution, frequency, severity, and course. AEs were assessed across all double-blind study visits and categorized according to body system for all participants who received at least one dose of patches (nicotine n = 12, placebo n = 13).
|
9.1%
1/11 • Number of events 1 • 8-Weeks
Adverse events were recorded and categorized by body system, event type, attribution, frequency, severity, and course. AEs were assessed across all double-blind study visits and categorized according to body system for all participants who received at least one dose of patches (nicotine n = 12, placebo n = 13).
|
|
General disorders
Insomnia
|
0.00%
0/11 • 8-Weeks
Adverse events were recorded and categorized by body system, event type, attribution, frequency, severity, and course. AEs were assessed across all double-blind study visits and categorized according to body system for all participants who received at least one dose of patches (nicotine n = 12, placebo n = 13).
|
9.1%
1/11 • Number of events 1 • 8-Weeks
Adverse events were recorded and categorized by body system, event type, attribution, frequency, severity, and course. AEs were assessed across all double-blind study visits and categorized according to body system for all participants who received at least one dose of patches (nicotine n = 12, placebo n = 13).
|
Additional Information
Dr. Paul A. Newhouse
Vanderbilt University Medical Center
Phone: (615) 327-7009
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place