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

This study has been completed.
Sponsor:
Collaborator:
McNeil Consumer & Specialty Pharmaceuticals, a Division of McNeil-PPC, Inc.
Information provided by (Responsible Party):
University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier:
NCT00377364
First received: September 14, 2006
Last updated: December 13, 2013
Last verified: December 2013
  Purpose

Studies in humans and animals support that stress and/or elevations in corticosteroids lead to changes in hippocampal structure and functioning. This is important as patients with major depression frequently have elevated cortisol, and millions of patients receive prescription corticosteroids (e.g. prednisone). Both depression and corticosteroid therapy are associated with memory impairment and hippocampal atrophy. Our research uses corticosteroid-treated patients to explore interventions that might protect the brain from the effects of stress or corticosteroids. We propose to give 30 corticosteroid-treated asthma patients acetaminophen or placebo. Between group differences in mood, memory and other neurocognitive measures will serve as outcome measures.


Condition Intervention Phase
Asthma
Rheumatic Disease
Drug: Drug: Acetaminophen, Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Acetaminophen for Mood and Memory Changes Associated With Prednisone Therapy

Resource links provided by NLM:


Further study details as provided by University of Texas Southwestern Medical Center:

Primary Outcome Measures:
  • Rey Auditory Verbal Learning Test (RAVLT) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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.

  • Rey Auditory Verbal Learning Task (RAVLT) [ Time Frame: Exit (Day 3 or Day 7) ] [ Designated as safety issue: No ]
    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.

  • Hamilton Rating Scale for Depression (HRSD-17) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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+).

  • Hamilton Rating Scale for Depression (HRSD-17) [ Time Frame: Exit (Day 3 or Day 7) ] [ Designated as safety issue: No ]
    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+).

  • Young Mania Rating Scale (YMRS) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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).

  • Young Mania Rating Scale (YMRS) [ Time Frame: Exit (Day 3 or Day 7) ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • Internal State Scale - Activation (ISS-ACT) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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.

  • Internal State Scale - Activation (ISS-ACT) [ Time Frame: Exit (Day 3 or Day 7) ] [ Designated as safety issue: No ]
    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.

  • Asthma Control Questionnaire (ACQ) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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).

  • Asthma Control Questionnaire [ Time Frame: Exit (Day 3 or Day 7) ] [ Designated as safety issue: No ]
    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).


Enrollment: 30
Study Start Date: November 2006
Study Completion Date: October 2008
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Acetaminophen
Participants will be given acetaminophen (two 500 mg tablets) four times daily for 7 days.
Drug: Drug: Acetaminophen, Drug: Placebo
Acetaminophen: Participants will be given acetaminophen (two 500 mg tablets) four times daily for 7 days, not exceeding 4,000 mg/day. Placebo: Participants will be given placebo(two 500 mg tablets) four times daily for 7 days
Other Name: Tylenol
Placebo Comparator: Placebo
Participants will be given an identical appearing placebo (two 500 mg tablets) four times daily for 7 days.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18-65
  • Scheduled to receive at least 20 mg/day of prednisone for at least 7 days
  • Baseline Rey Auditory Verbal Learning Test (RAVLT) total score of ≥40

Exclusion Criteria:

  • History of allergic reaction or other contraindication to acetaminophen therapy
  • Acetaminophen use within 24 hours of study entry
  • History of liver disease or alcohol use of greater than 3 drinks/day
  • Severe or unstable medical condition (e.g., recent myocardial infarction,renal failure, diabetes with poor glycemic control)
  • Pregnant or lactating female
  • Patient has mental retardation, dementia, or other severe cognitive disorder
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00377364

Locations
United States, Texas
UT Southwestern Medical Center at Dallas
Dallas, Texas, United States, 75390
Sponsors and Collaborators
University of Texas Southwestern Medical Center
McNeil Consumer & Specialty Pharmaceuticals, a Division of McNeil-PPC, Inc.
Investigators
Principal Investigator: Edson S Brown, M.D., PhD UT Southwestern Medical Center at Dallas
  More Information

Additional Information:
No publications provided

Responsible Party: University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT00377364     History of Changes
Other Study ID Numbers: 022006-009
Study First Received: September 14, 2006
Results First Received: August 19, 2011
Last Updated: December 13, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Texas Southwestern Medical Center:
Acetaminophen
corticosteroids
prednisone

Additional relevant MeSH terms:
Asthma
Rheumatic Diseases
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Musculoskeletal Diseases
Connective Tissue Diseases
Acetaminophen
Prednisone
Antipyretics
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on July 22, 2014