Effect of Nuvigil on Fatigue

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT01460628
• Collaborator: Teva Pharmaceuticals USA (Industry)
• Enrollment: 25
• Location: 1
• Arm: 1
• Duration (Months): 26
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if armodafinil improves quality of life and is an effective treatment of fatigue in symptomatic perimenopausal and postmenopausal women.

Condition or Disease	Intervention/Treatment	Phase
Menopause	Drug: Armodafinil	Phase 4

Detailed Description

Fatigue is one of the most prevalent symptoms occurring in peri- and postmenopausal women. It is strongly associated with reduced quality of life in this population. Studies have shown a strong association between fatigue and menopausal symptoms such as hot flashes, vaginal symptoms, and sexual dysfunction. Because sleep disturbance commonly co-occurs in women with hot flashes as a result of nocturnal hot flashes disrupting sleep, sleep disturbance may explain the association between hot flashes and fatigue in this population. However evidence suggests that fatigue can occur in the absence of sleep disruption, indicating that sleep problems do not exclusively explain the etiology of fatigue in this population.

Armodafinil is a wakefulness-promoting agent that acts as a central nervous system stimulant. It is chemically and pharmacologically unrelated to other CNS stimulants, such as methylphenidate and amphetamine. Armodafinil is FDA approved to increase wakefulness in patients with excessive sleepiness due to narcolepsy, obstructive sleep apnea, and shift work sleep disorder. It has not be studied in menopause-associated fatigue.

In the proposed study, the investigators plan to investigate the effect of armodafinil on quality of life and fatigue in a population of peri- and postmenopausal women with fatigue and reduced quality of life who do not have primary sleep disorders, significant levels of insomnia, or depression.

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The Effect of Armodafinil (Nuvigil) on Fatigue and Quality of Life in Peri- and Postmenopausal Women
• Study Start Date: Oct 1, 2011
• Actual Primary Completion Date: May 1, 2013
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Armodafinil Armodafinil is the drug being tested.

Drug: Armodafinil; Women who are eligible will receive 4 weeks of treatment with armodafinil. Armodafinil will be titrated from 50-mg/day up to 150-mg/day. For exploratory reasons only, at the end of the 4-week treatment period, participants will enter a discontinuation phase in which they will be randomized to double-blind treatment with armodafinil 150-mg/day or matching placebo for 2 weeks in a 1-to-1 ratio. No primary outcomes were studied in the discontinuation phase.; Other Names: Nuvigil

Outcome Measures

Primary Outcome Measures

1. Menopause Quality Of Life Questionnaire (MENQOL) Physical Domain Subscale [4 weeks]

   This is a widely used self-report instrument to determine differences in quality of life among menopausal women and to measure changes in their quality of life over time. Four domain scores are calculated from the 29-item instrument. The physical domain subscale has 16 questions and a range from 0-8 with higher scores indicating worse symptoms.

2. Brief Fatigue Inventory (BFI) [4 weeks]

   This is a widely used self-report instrument to assess the severity of fatigue and the impact of fatigue on daily functioning. This 9 item instrument yields a global fatigue score ranging from 0-10 with higher scores indicating worse symptoms. .

Secondary Outcome Measures

1. Epsworth Sleepiness Scale (ESS) [4 weeks]

   This self-report scale is widely used as a subjective measure of sleepiness. This 8 item instrument yields a total score ranging from 0-24 with higher scores indicating worse symptoms.

2. Hot Flash Frequency (24-hr Period) [4 weeks]

   The Daily Vasomotor Symptom Diary consists of a 7-day scale on which the subject records the total number of hot flushes they experience on a daily basis. Weekly averages for a 24-hour period are calculated.

3. Symptom Checklist-10 Anxiety [4 weeks]

   The SCL-10 anxiety subscale, developed from the refinement of the Hopkins Symptom Checklist (HSCL), consists of 10 questions focused on how much discomfort symptoms of anxiety (e.g. "nervousness or shaking inside") have caused in the past two weeks. Each question is answered on a scale from 0-4, and answers are averaged for a total score between 0-4 with higher scores indicating more anxiety.

4. Patient Health Questionnaire-9 (PHQ-9) [4 weeks]

   The PHQ-9 is the self-administered form of the Primary Care Evaluation of Mental Disorders (PRIME-MD), a widely used instrument designed to screen for psychiatric illnesses in primary-care settings. This 9-item instrument assesses mood, depressive symptoms, and suicidal ideation. The range of total scores is 0-27 with higher scores indicating worse symptoms. Generally, scores 5-9 indicate mild depression, 10-14 indicate moderate depression, and 15+ indicate moderately severe or severe depression.

5. Brown Attention Deficit Disorder Scale (BADDS) [4 weeks]

   This is a normed and validated measure of ADHD-related executive function impairments. The clinician administered scale measures five clusters of executive function including 1) organizing and activating for work, 2) sustaining attention and concentration, 3) sustaining alertness, effort, and processing speed, 4) managing affective interference, and 5) using working memory and accessing recall. The frequency and severity of each of the 40 items is rated on a scale of 0 to 3, with the total scores ranging from 0-120 and higher scores indicating worse symptoms.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 65 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

Women

• Ages 40-65

• Peri- and postmenopausal

• Suffering from fatigue

• Experiencing hot flashes(Not required for perimenopausal women)

Exclusion Criteria:

• Current episode of major depression

• Moderate-to-severe insomnia

• Night shift workers

• Previous diagnosis of manic depressive disorder, psychotic disorder, or psychotic symptoms

• Suicidal ideation

• Alcohol/drug abuse

• Concern about potential misuse of study medication

• Use of prescribed medications to treat insomnia or other sleep disturbance symptoms

• Pregnant or breastfeeding

• Use of systemic menopausal hormonal therapy or birth control

• Use of centrally active medications, such as antidepressants, anxiolytics, and hypnotics agents

• Use of clopidogrel

• Use of atomoxetine

• Cardiovascular contraindications of use of armodafinil

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• Massachusetts General Hospital
• Teva Pharmaceuticals USA

Investigators

• Principal Investigator: Hadine Joffe, MD, MSc, Brigham and Women's Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hadine Joffe, MD, Vice Chair for Research, Psychiatry Department, Brigham and Women's Hospital
• ClinicalTrials.gov Identifier: NCT01460628
• Other Study ID Numbers: 2011P-001055
• First Posted: Oct 27, 2011
• Last Update Posted: Mar 15, 2017
• Last Verified: Jan 1, 2017

• Keywords provided by Hadine Joffe, MD, Vice Chair for Research, Psychiatry Department, Brigham and Women's Hospital: fatigue; menopausal symptoms; hot flashes; Vasomotor symptoms; perimenopause; related Quality of life
• Additional relevant MeSH terms: Fatigue; Modafinil

Study Results

Participant Flow

Arm/Group Title	Armodafinil
Arm/Group Description	Armodafinil is the drug being tested. Women who are eligible will receive 4 weeks of treatment with armodafinil. Armodafinil will be titrated from 50-mg/day up to 150-mg/day. For exploratory reasons only, at the end of the 4-week treatment period, participants will enter a discontinuation phase in which they will be randomized to double-blind treatment with armodafinil 150-mg/day or matching placebo for 2 weeks in a 1-to-1 ratio.
Period Title: Overall Study
STARTED	25
COMPLETED	20
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Armodafinil
Arm/Group Description	Armodafinil is the drug being tested. Women who are eligible will receive 4 weeks of treatment with armodafinil. Armodafinil will be titrated from 50-mg/day up to 150-mg/day. For exploratory reasons only, at the end of the 4-week treatment period, participants will enter a discontinuation phase in which they will be randomized to double-blind treatment with armodafinil 150-mg/day or matching placebo for 2 weeks in a 1-to-1 ratio.
Overall Participants	25
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.8 (5.13)
Sex: Female, Male (Count of Participants)
Female	25 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	25 100%

Outcome Measures

1. Primary Outcome

Title	Menopause Quality Of Life Questionnaire (MENQOL) Physical Domain Subscale
Description	This is a widely used self-report instrument to determine differences in quality of life among menopausal women and to measure changes in their quality of life over time. Four domain scores are calculated from the 29-item instrument. The physical domain subscale has 16 questions and a range from 0-8 with higher scores indicating worse symptoms.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Armodafinil
Arm/Group Description	Armodafinil is the drug being tested. Women who are eligible will receive 4 weeks of treatment with armodafinil. Armodafinil will be titrated from 50-mg/day up to 150-mg/day. For exploratory reasons only, at the end of the 4-week treatment period, participants will enter a discontinuation phase in which they will be randomized to double-blind treatment with armodafinil 150-mg/day or matching placebo for 2 weeks in a 1-to-1 ratio.
Measure Participants	20
Median (Inter-Quartile Range) [units on a scale]	1.9

2. Primary Outcome

Title	Brief Fatigue Inventory (BFI)
Description	This is a widely used self-report instrument to assess the severity of fatigue and the impact of fatigue on daily functioning. This 9 item instrument yields a global fatigue score ranging from 0-10 with higher scores indicating worse symptoms. .
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Armodafinil
Arm/Group Description	Armodafinil is the drug being tested. Women who are eligible will receive 4 weeks of treatment with armodafinil. Armodafinil will be titrated from 50-mg/day up to 150-mg/day. For exploratory reasons only, at the end of the 4-week treatment period, participants will enter a discontinuation phase in which they will be randomized to double-blind treatment with armodafinil 150-mg/day or matching placebo for 2 weeks in a 1-to-1 ratio.
Measure Participants	20
Median (Inter-Quartile Range) [units on a scale]	2.2

3. Secondary Outcome

Title	Epsworth Sleepiness Scale (ESS)
Description	This self-report scale is widely used as a subjective measure of sleepiness. This 8 item instrument yields a total score ranging from 0-24 with higher scores indicating worse symptoms.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Armodafinil
Arm/Group Description	Armodafinil is the drug being tested. Women who are eligible will receive 4 weeks of treatment with armodafinil. Armodafinil will be titrated from 50-mg/day up to 150-mg/day. For exploratory reasons only, at the end of the 4-week treatment period, participants will enter a discontinuation phase in which they will be randomized to double-blind treatment with armodafinil 150-mg/day or matching placebo for 2 weeks in a 1-to-1 ratio.
Measure Participants	20
Median (Inter-Quartile Range) [units on a scale]	3.0

4. Secondary Outcome

Title	Hot Flash Frequency (24-hr Period)
Description	The Daily Vasomotor Symptom Diary consists of a 7-day scale on which the subject records the total number of hot flushes they experience on a daily basis. Weekly averages for a 24-hour period are calculated.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Armodafinil
Arm/Group Description	Armodafinil is the drug being tested. Women who are eligible will receive 4 weeks of treatment with armodafinil. Armodafinil will be titrated from 50-mg/day up to 150-mg/day. For exploratory reasons only, at the end of the 4-week treatment period, participants will enter a discontinuation phase in which they will be randomized to double-blind treatment with armodafinil 150-mg/day or matching placebo for 2 weeks in a 1-to-1 ratio.
Measure Participants	20
Median (Inter-Quartile Range) [# of hot flashes]	1.5

5. Secondary Outcome

Title	Symptom Checklist-10 Anxiety
Description	The SCL-10 anxiety subscale, developed from the refinement of the Hopkins Symptom Checklist (HSCL), consists of 10 questions focused on how much discomfort symptoms of anxiety (e.g. "nervousness or shaking inside") have caused in the past two weeks. Each question is answered on a scale from 0-4, and answers are averaged for a total score between 0-4 with higher scores indicating more anxiety.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Armodafinil
Arm/Group Description	Armodafinil is the drug being tested. Women who are eligible will receive 4 weeks of treatment with armodafinil. Armodafinil will be titrated from 50-mg/day up to 150-mg/day. For exploratory reasons only, at the end of the 4-week treatment period, participants will enter a discontinuation phase in which they will be randomized to double-blind treatment with armodafinil 150-mg/day or matching placebo for 2 weeks in a 1-to-1 ratio.
Measure Participants	20
Median (Inter-Quartile Range) [units on a scale]	0

6. Secondary Outcome

Title	Patient Health Questionnaire-9 (PHQ-9)
Description	The PHQ-9 is the self-administered form of the Primary Care Evaluation of Mental Disorders (PRIME-MD), a widely used instrument designed to screen for psychiatric illnesses in primary-care settings. This 9-item instrument assesses mood, depressive symptoms, and suicidal ideation. The range of total scores is 0-27 with higher scores indicating worse symptoms. Generally, scores 5-9 indicate mild depression, 10-14 indicate moderate depression, and 15+ indicate moderately severe or severe depression.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Armodafinil
Arm/Group Description	Armodafinil is the drug being tested. Women who are eligible will receive 4 weeks of treatment with armodafinil. Armodafinil will be titrated from 50-mg/day up to 150-mg/day. For exploratory reasons only, at the end of the 4-week treatment period, participants will enter a discontinuation phase in which they will be randomized to double-blind treatment with armodafinil 150-mg/day or matching placebo for 2 weeks in a 1-to-1 ratio.
Measure Participants	20
Median (Inter-Quartile Range) [units on a scale]	3.0

7. Secondary Outcome

Title	Brown Attention Deficit Disorder Scale (BADDS)
Description	This is a normed and validated measure of ADHD-related executive function impairments. The clinician administered scale measures five clusters of executive function including 1) organizing and activating for work, 2) sustaining attention and concentration, 3) sustaining alertness, effort, and processing speed, 4) managing affective interference, and 5) using working memory and accessing recall. The frequency and severity of each of the 40 items is rated on a scale of 0 to 3, with the total scores ranging from 0-120 and higher scores indicating worse symptoms.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Armodafinil
Arm/Group Description	Armodafinil is the drug being tested. Women who are eligible will receive 4 weeks of treatment with armodafinil. Armodafinil will be titrated from 50-mg/day up to 150-mg/day. For exploratory reasons only, at the end of the 4-week treatment period, participants will enter a discontinuation phase in which they will be randomized to double-blind treatment with armodafinil 150-mg/day or matching placebo for 2 weeks in a 1-to-1 ratio.
Measure Participants	20
Median (Inter-Quartile Range) [units on a scale]	15.5

Adverse Events

Arm/Group Title	Armodafinil
Arm/Group Description	Armodafinil is the drug being tested. Women who are eligible will receive 4 weeks of treatment with armodafinil. Armodafinil will be titrated from 50-mg/day up to 150-mg/day. For exploratory reasons only, at the end of the 4-week treatment period, participants will enter a discontinuation phase in which they will be randomized to double-blind treatment with armodafinil 150-mg/day or matching placebo for 2 weeks in a 1-to-1 ratio.
All Cause Mortality
	Armodafinil
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Armodafinil
	Affected / at Risk (%)	# Events
Total	0/25 (0%)
Other (Not Including Serious) Adverse Events
	Armodafinil
	Affected / at Risk (%)	# Events
Total	16/25 (64%)
Cardiac disorders
increased blood pressure or heartbeat	4/25 (16%)	4
Ear and labyrinth disorders
dry mouth	3/25 (12%)	4
dizziness	1/25 (4%)	1
Gastrointestinal disorders
stomach ache/nausea/gas	7/25 (28%)	9
constipation/diarrhea	4/25 (16%)	4
Metabolism and nutrition disorders
increased appetite	1/25 (4%)	1
Musculoskeletal and connective tissue disorders
jaw clenching	1/25 (4%)	2
Nervous system disorders
headache	3/25 (12%)	3
sleep disruption	4/25 (16%)	5
jitteriness	1/25 (4%)	1
word recall	1/25 (4%)	1
Psychiatric disorders
depression/anxiety	8/25 (32%)	9
Reproductive system and breast disorders
spotting	1/25 (4%)	1
Respiratory, thoracic and mediastinal disorders
upper respiratory symptoms	5/25 (20%)	7
Skin and subcutaneous tissue disorders
skin irritation	3/25 (12%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.