Trial Outcomes & Findings for Acetaminophen (Tylenol) for Mood and Memory Changes Associated With Corticosteroid Therapy (NCT NCT00377364)

NCT ID: NCT00377364

Last Updated: 2016-05-05

Results Overview

This is a measure of declarative memory (associated with the hippocampus), using the mean number of words (0-75) recalled from Trials I-V of the RAVLT ± the standard deviation. The assessement was conducted using the same procedures as at baseline. RAVLT total score of ≥ 40 words on trials 1-5(from a range of 0 to 75 words possible)suggests relatively normal memory prior to prednisone therapy.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 30 participants
• Primary outcome timeframe: Exit (Day 3 or Day 7)
• Results posted on: 2016-05-05

Participant Flow

This randomized, double-blind, placebo-controlled study was conducted at asthma and allergy clinics on the UT Southwestern Medical Center campus.

Those with prior psychiatric symptoms during corticosteroid therapy were not excluded.

Participant milestones

Measure	Acetaminophen OTC pain reliever.fever reducer that may have neuroprotective effects.	Placebo Matching Placebo.
Overall Study STARTED	16	14
Overall Study COMPLETED	14	14
Overall Study NOT COMPLETED	2	0

Reasons for withdrawal

Measure	Acetaminophen OTC pain reliever.fever reducer that may have neuroprotective effects.	Placebo Matching Placebo.
Overall Study Lost to Follow-up	1	0
Overall Study Withdrawal by Subject	1	0

Baseline Characteristics

Acetaminophen (Tylenol) for Mood and Memory Changes Associated With Corticosteroid Therapy

Baseline characteristics by cohort

Measure	Acetaminophen n=16 Participants OTC pain reliever.fever reducer that may have neuroprotective effects.	Placebo n=14 Participants Matching Placebo.	Total n=30 Participants Total of all reporting groups
Age, Continuous	46.4 years STANDARD_DEVIATION 10.4 • n=5 Participants	39.8 years STANDARD_DEVIATION 11.6 • n=7 Participants	43.3 years STANDARD_DEVIATION 11.3 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	12 Participants n=7 Participants	22 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 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	10 Participants n=5 Participants	8 Participants n=7 Participants	18 Participants n=5 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Region of Enrollment United States	16 participants n=5 Participants	14 participants n=7 Participants	30 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline

This is a measure of declarative memory (associated with the hippocampus). The test consists of 15 nouns read aloud for five consecutive trials with each trial followed by a free-recall trial. Following the fifth trial, an interference list of 15 different words is presented followed by a free-recall trial of that list. Delayed recall of the first list is tested immediately following the interference list and after a 20-minute delay. A recognition test of 50 words including the 15 original words is presented after the delayed recall. RAVLT total score of ≥ 40 words on trials 1-5(from a range of 0 to 75 words possible)suggests relatively normal memory prior to prednisone therapy.

Outcome measures

Measure	Acetaminophen n=14 Participants OTC pain reliever and fever reducer that may have neuroprotective effects.	Placebo n=14 Participants Matching Placebo.
Rey Auditory Verbal Learning Test (RAVLT)	44.8 words Standard Deviation 4.7	44.1 words Standard Deviation 9.3

PRIMARY outcome

Timeframe: Exit (Day 3 or Day 7)

Population: ITT defined as any post baseline visit. Last Observation Carried Forward.

This is a measure of declarative memory (associated with the hippocampus), using the mean number of words (0-75) recalled from Trials I-V of the RAVLT ± the standard deviation. The assessement was conducted using the same procedures as at baseline. RAVLT total score of ≥ 40 words on trials 1-5(from a range of 0 to 75 words possible)suggests relatively normal memory prior to prednisone therapy.

Outcome measures

Measure	Acetaminophen n=14 Participants OTC pain reliever and fever reducer that may have neuroprotective effects.	Placebo n=14 Participants Matching Placebo.
Rey Auditory Verbal Learning Task (RAVLT)	44.9 words Standard Deviation 10.9	44.9 words Standard Deviation 11.2

PRIMARY outcome

Timeframe: Baseline

The assessment is a clinician administered rating of depression with 17 questions. The total score is indicates level of depression within the following ranges: none (0-5), mild (6-10), moderate (11-15), severe (16-20), and very severe (21+).

Outcome measures

Measure	Acetaminophen n=14 Participants OTC pain reliever and fever reducer that may have neuroprotective effects.	Placebo n=14 Participants Matching Placebo.
Hamilton Rating Scale for Depression (HRSD-17)	11.3 units on a scale Standard Deviation 6.5	13.4 units on a scale Standard Deviation 8.6

PRIMARY outcome

Timeframe: Exit (Day 3 or Day 7)

Population: ITT defined as any post baseline visit. Last Observation Carried Forward.

The assessment is a clinician administered rating of depression with 17 questions. The total score is indicates level of depression within the following ranges: none (0-5), mild (6-10), moderate (11-15), severe (16-20), and very severe (21+).

Outcome measures

Measure	Acetaminophen n=14 Participants OTC pain reliever and fever reducer that may have neuroprotective effects.	Placebo n=14 Participants Matching Placebo.
Hamilton Rating Scale for Depression (HRSD-17)	8.3 units on a scale Standard Deviation 6.5	10.3 units on a scale Standard Deviation 8.4

PRIMARY outcome

Timeframe: Baseline

This is an 11-item, observer rated measure of the severity of manic symptoms on a 5 point scale. The total score indicates overall severity of mania with a minimum of zero (indicating normalcy) and a maximum of 60 (indicating very severe).

Outcome measures

Measure	Acetaminophen n=14 Participants OTC pain reliever and fever reducer that may have neuroprotective effects.	Placebo n=14 Participants Matching Placebo.
Young Mania Rating Scale (YMRS)	5.8 units on a scale Standard Deviation 2.2	6.1 units on a scale Standard Deviation 5.4

PRIMARY outcome

Timeframe: Exit (Day 3 or Day 7)

Population: ITT defined as any post baseline visit. Last Observation Carried Forward.

This is an 11-item, observer rated measure of the severity of manic symptoms on a 5 point scale. The total score indicates overall severity of mania with a minimum of zero (indicating normalcy) and a maximum of 60 (indicating very severe).

Outcome measures

Measure	Acetaminophen n=14 Participants OTC pain reliever and fever reducer that may have neuroprotective effects.	Placebo n=14 Participants Matching Placebo.
Young Mania Rating Scale (YMRS)	5.9 units on a scale Standard Deviation 5.8	5.6 units on a scale Standard Deviation 5.4

SECONDARY outcome

Timeframe: Baseline

Activation subscale assesses (hypo)manic symptoms. There are 16 questions on the total ISS, each rated on a series of visual analogue scale (VAS) items consisting of statement followed by a 100 mm line with anchor points at 0 and 100. The 16 questions divide into four subscales measuring activation; depression, global psychopathology, and well being. Depression Index (DI): Scores for items 7 and 9 are added to give a DI score ranging from 0-200 with 0 being absence of depressive symptoms and 200 indicating severe depressive symptoms. Well-Being Index (WB): Scores for items 3, 5 and 15 are added to give a WB score ranging form 0-300, with >125 indicating euthymia. Activation Index (ACT): Scores for items 6, 8, 10, 12 and 13 are added to give an ACT score ranging from 0-500, with >155 indicating mania. Perceived Conflict Index (PC): Scores for items 1, 2, 4, 11 and 14 are added to give a PC score ranging from 0-500, with higher scores indicating greater severity of psychopathology.

Outcome measures

Measure	Acetaminophen n=14 Participants OTC pain reliever and fever reducer that may have neuroprotective effects.	Placebo n=14 Participants Matching Placebo.
Internal State Scale - Activation (ISS-ACT)	58.0 units on a scale Standard Deviation 53.8	109.6 units on a scale Standard Deviation 82.3

SECONDARY outcome

Timeframe: Exit (Day 3 or Day 7)

Population: ITT defined as any post baseline visit. Last Observation Carried Forward.

Activation subscale assesses (hypo)manic symptoms. There are 16 questions on the total ISS, each rated on a series of visual analogue scale (VAS) items consisting of statement followed by a 100 mm line with anchor points at 0 and 100. The 16 questions divide into four subscales measuring activation; depression, global psychopathology, and well being. Depression Index (DI): Scores for items 7 and 9 are added to give a DI score ranging from 0-200 with 0 being absence of depressive symptoms and 200 indicating severe depressive symptoms. Well-Being Index (WB): Scores for items 3, 5 and 15 are added to give a WB score ranging form 0-300, with >125 indicating euthymia. Activation Index (ACT): Scores for items 6, 8, 10, 12 and 13 are added to give an ACT score ranging from 0-500, with >155 indicating mania. Perceived Conflict Index (PC): Scores for items 1, 2, 4, 11 and 14 are added to give a PC score ranging from 0-500, with higher scores indicating greater severity of psychopathology.

Outcome measures

Measure	Acetaminophen n=14 Participants OTC pain reliever and fever reducer that may have neuroprotective effects.	Placebo n=14 Participants Matching Placebo.
Internal State Scale - Activation (ISS-ACT)	93.5 units on a scale Standard Deviation 98.2	107.8 units on a scale Standard Deviation 121.0

SECONDARY outcome

Timeframe: Baseline

This is a seven item assessment of symptoms pertinent to asthma management, including day and nighttime symptoms; activity limitation; use of prn bronchodilators; a physiological measure of asthma (spirometry), forced expiratory volume in 1 second percent predicted (FEV1% predicted), which is the percentile of FEV1 compared to normal controls matched for age, height, gender, and race, in the scoring. Total mean is interpreted on a scale between 0 (asthma completely controlled) and 6 (asthma severely uncontrolled).

Outcome measures

Measure	Acetaminophen n=14 Participants OTC pain reliever and fever reducer that may have neuroprotective effects.	Placebo n=14 Participants Matching Placebo.
Asthma Control Questionnaire (ACQ)	3.1 units on a scale Standard Deviation 1.0	3.3 units on a scale Standard Deviation 1.3

SECONDARY outcome

Timeframe: Exit (Day 3 or Day 7)

Population: ITT defined as any post baseline visit. Last Observation Carried Forward.

This is a seven item assessment of symptoms pertinent to asthma management, including day and nighttime symptoms; activity limitation; use of prn bronchodilators; a physiological measure of asthma (spirometry), forced expiratory volume in 1 second percent predicted (FEV1% predicted), which is the percentile of FEV1 compared to normal controls matched for age, height, gender, and race, in the scoring. Total mean is interpreted on a scale between 0 (asthma completely controlled) and 6 (asthma severely uncontrolled).

Outcome measures

Measure	Acetaminophen n=14 Participants OTC pain reliever and fever reducer that may have neuroprotective effects.	Placebo n=14 Participants Matching Placebo.
Asthma Control Questionnaire	1.9 units on a scale Standard Deviation 1.6	1.7 units on a scale Standard Deviation 1.4

Adverse Events

Acetaminophen

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

E.Sherwood Brown, M.D., Ph.D.

UT Southwetern Medical Center at Dallas

Phone: 214-645-6950

Email: Sherwood.Brown@utsouthwestern.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place