Double Blind Trial of Duloxetine in Chronic Fatigue Syndrome (CFS)
Primary Purpose
Fatigue Syndrome, Chronic
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Duloxetine
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Fatigue Syndrome, Chronic focused on measuring Fatigue, Fatigue syndrome, chronic, Chronic fatigue syndrome, CFS, Fibromyalgia
Eligibility Criteria
Inclusion Criteria:
- Female and male outpatients between 18-65 years of age.
- Meet criteria for revised Center for Disease Control (CDC) definition of Chronic Fatigue Syndrome (CFS) (at least 6 months of persistent fatigue that substantially reduces the person's level of activity; 4 or more of the following symptoms that must occur with fatigue in a 6-month period: impaired memory or concentration, sore throat, tender glands, aching or stiff muscles, multijoint pain, new headaches, unrefreshing sleep, and post-exertional fatigue. Medical conditions that may explain the fatigue and psychiatric disorders, including eating disorders, psychotic disorders, bipolar disorder, melancholic depression, and substance abuse within 2 years of the onset of fatigue, are excluded).
- Provision of written informed consent for participation in the trial.
- Educational level and degree of understanding such that the patient can communicate intelligibly with the investigator and study staff.
- Judged to be reliable and agree to keep all appointments for clinic visits, tests, and procedures required by the protocol.
Exclusion Criteria:
- Current melancholic major depressive disorder, or a previous diagnosis of psychosis, eating disorder, or bipolar disorder.
- History of substance abuse or dependence within the past year, excluding nicotine and caffeine.
- A positive urine drug screen for any substance of abuse (may be retested if positive test was for a prescribed medication that was not washed out).
- Women who are pregnant or breast feeding; women must test negative for pregnancy at Visit 1.
- Women of childbearing potential who are not using a medically accepted means of contraceptive when engaging in sexual intercourse.
- Patients who, in the opinion of the investigator, are treatment-refractory or whose response is likely to be compromised by existing or future disability compensation issues.
- Serious unstable medical illness, including cardiovascular, hepatic, renal, respiratory, or hematologic illness, or other unstable medical or psychiatric conditions that in the opinion of the investigator would compromise participation or would likely lead to hospitalization during the duration of the study. Abnormal thyroid stimulating hormone (TSH) concentrations (unless treatment for hypothyroidism has been stable for at least the past 3 months and the patient is clinically euthyroid).
- Patients who have uncontrolled narrow-angle glaucoma.
- Patients who have acute liver injury (such as hepatitis) or severe cirrhosis (Child-Pugh Class C).
- Patients who are judged prior to randomization to be at suicidal risk by the clinical investigator.
- Treatment with antidepressant medication within 14 days prior to randomization with the exception of fluoxetine, which cannot be used within 30 days prior to randomization. Potential need to use a monoamine oxidase inhibitor (MAOI) during the study or within 2 weeks of discontinuation of study treatment.
- Patients who have previously taken duloxetine
- Patients who are taking any excluded medications that cannot be discontinued at Visit 1.
- Treatment within the last 30 days with a drug that has not received regulatory approval at the time of study entry.
- Known hypersensitivity to duloxetine or any of the inactive ingredients.
Sites / Locations
- Women's Health Research Program
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Duloxetine
Placebo
Arm Description
Duloxetine po 60-120 mg/day for 12 weeks
Placebo comparator to Duloxetine
Outcomes
Primary Outcome Measures
Change From Baseline in Multidimensional Fatigue Inventory (MFI)--General Fatigue Subscale Score
The MFI is a self-reported instrument that contains 20 statements covering different aspects of fatigue. The MFI consists of 5 subscales: general fatigue, physical fatigue, mental fatigue, reduced activity, and reduced concentration. Each subscale includes 4 items with 5-point Likert scales. Scores on each subscale range from 4-20 with higher scores indicating greater fatigue. A decrease in the score indicates improvement.
The general fatigue subscale (primary measure) includes general statements about tiredness, feeling rested, and overall feelings of being fit.
Secondary Outcome Measures
Change From Baseline in Brief Pain Inventory (BPI) --Average Pain Severity Score
The BPI is a self-administered scale that measures the severity of pain. Pain severity is rated on a 0 [no pain] to 10 [pain as bad a you can imagine] scale. Average pain is rated over the previous 24 hours. Higher scores indicate greater pain severity. A decrease in the score indicates improvement (i.e. decrease in pain severity).
Change From Baseline in the Hospital Anxiety and Depression Scale (HADS) --Depression Subscale
The HADS is a self-reported instrument designed as a brief assessment tool of anxiety and depression in nonpsychiatric populations. It is a 14-item questionnaire that consistes of 2 subscales of 7 items designed to measure levels of both anxiety and depression. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 and 21 for either anxiety or depression. Higher scores indicate greater levels of anxiety or depression. A decrease in the score indicates improvement.
Change From Baseline in the Clinical Global Impression of Severity (CGI-S)
Clinician rated assessment of severity on a 1 (normal)-7 (extremely ill) scale. A decrease in the score indicates improvement.
Patient Global Impression of Improvement (PGI-I)
Patient rated assessment of change on a 1 (very much better) to 7 (very much worse) scale.
Number of Participants Who Discontinued the Study for Any Reason
Description of discontinuation rates of participants; all participants who dropped out of the study after randomization were included. The reasons for drop outs included lack of efficacy, adverse event, lost to follow-up, personal conflict or other patient decision, withdrawal of informed consent, and non-compliance.
Number of Participants Who Discontinued Use of Treatment Due to Adverse Events
Paticipants who dropped out of the study because of intolerable adverse events.
Full Information
NCT ID
NCT00375973
First Posted
September 12, 2006
Last Updated
July 31, 2015
Sponsor
University of Cincinnati
Collaborators
Eli Lilly and Company
1. Study Identification
Unique Protocol Identification Number
NCT00375973
Brief Title
Double Blind Trial of Duloxetine in Chronic Fatigue Syndrome
Acronym
CFS
Official Title
A Randomized, Placebo-Controlled, Double-Blind Trial of Duloxetine in the Treatment of Patients With Chronic Fatigue Syndrome
Study Type
Interventional
2. Study Status
Record Verification Date
July 2015
Overall Recruitment Status
Completed
Study Start Date
September 2006 (undefined)
Primary Completion Date
June 2012 (Actual)
Study Completion Date
March 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Cincinnati
Collaborators
Eli Lilly and Company
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to determine the safety and efficacy of duloxetine compared with placebo for reducing fatigue in patients diagnosed with Chronic Fatigue Syndrome (CFS).
Detailed Description
Chronic fatigue syndrome (CFS) is characterized by severe disabling fatigue of at least six months duration that cannot be fully explained by an identifiable medical condition . Pain symptoms are also a part of the diagnostic criteria for CFS, and include muscle pain, multi-joint pain, and headaches. The prevalence of CFS ranges from 0.007 to 2.8 % in the general adult population and 0.006 to 3.0% in primary care practice (2). Although most who receive a CFS diagnosis are 30-40 years of age, Caucasian, and female, CFS affects both women and men, adults and children, and all racial and socioeconomic classes.
Patients with CFS have 2-4 times the rate of depression and anxiety compared with the general population. CFS is also commonly comorbid with fibromyalgia, a disorder characterized by chronic widespread pain, tenderness, fatigue, sleep and mood disturbances. In some samples, 70% of patients with fibromyalgia also meet criteria for CFS. CFS and fibromyalgia are characterized by greater similarities than differences and may share pathophysiologic features. Like fibromyalgia, CFS is associated with chronic pain, sleep and mood disturbances. Because fibromyalgia responds to treatment with antidepressants, particularly the dual serotonin and norepinephrine reuptake inhibitors, including duloxetine, antidepressant trials in CFS are clearly needed.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fatigue Syndrome, Chronic
Keywords
Fatigue, Fatigue syndrome, chronic, Chronic fatigue syndrome, CFS, Fibromyalgia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
60 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Duloxetine
Arm Type
Experimental
Arm Description
Duloxetine po 60-120 mg/day for 12 weeks
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo comparator to Duloxetine
Intervention Type
Drug
Intervention Name(s)
Duloxetine
Other Intervention Name(s)
Cymbalta
Intervention Description
Duloxetine po 60-120 mg/day for 12 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Sugar Pill
Intervention Description
Sugar pill dose comparable to duloxetine
Primary Outcome Measure Information:
Title
Change From Baseline in Multidimensional Fatigue Inventory (MFI)--General Fatigue Subscale Score
Description
The MFI is a self-reported instrument that contains 20 statements covering different aspects of fatigue. The MFI consists of 5 subscales: general fatigue, physical fatigue, mental fatigue, reduced activity, and reduced concentration. Each subscale includes 4 items with 5-point Likert scales. Scores on each subscale range from 4-20 with higher scores indicating greater fatigue. A decrease in the score indicates improvement.
The general fatigue subscale (primary measure) includes general statements about tiredness, feeling rested, and overall feelings of being fit.
Time Frame
Baseline to endpoint at 12 weeks
Secondary Outcome Measure Information:
Title
Change From Baseline in Brief Pain Inventory (BPI) --Average Pain Severity Score
Description
The BPI is a self-administered scale that measures the severity of pain. Pain severity is rated on a 0 [no pain] to 10 [pain as bad a you can imagine] scale. Average pain is rated over the previous 24 hours. Higher scores indicate greater pain severity. A decrease in the score indicates improvement (i.e. decrease in pain severity).
Time Frame
Baseline to endpoint at 12 weeks
Title
Change From Baseline in the Hospital Anxiety and Depression Scale (HADS) --Depression Subscale
Description
The HADS is a self-reported instrument designed as a brief assessment tool of anxiety and depression in nonpsychiatric populations. It is a 14-item questionnaire that consistes of 2 subscales of 7 items designed to measure levels of both anxiety and depression. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 and 21 for either anxiety or depression. Higher scores indicate greater levels of anxiety or depression. A decrease in the score indicates improvement.
Time Frame
baseline to endpoint at 12 weeks
Title
Change From Baseline in the Clinical Global Impression of Severity (CGI-S)
Description
Clinician rated assessment of severity on a 1 (normal)-7 (extremely ill) scale. A decrease in the score indicates improvement.
Time Frame
baseline to endpoint at 12 weeks
Title
Patient Global Impression of Improvement (PGI-I)
Description
Patient rated assessment of change on a 1 (very much better) to 7 (very much worse) scale.
Time Frame
baseline to endpoint at 12 weeks.
Title
Number of Participants Who Discontinued the Study for Any Reason
Description
Description of discontinuation rates of participants; all participants who dropped out of the study after randomization were included. The reasons for drop outs included lack of efficacy, adverse event, lost to follow-up, personal conflict or other patient decision, withdrawal of informed consent, and non-compliance.
Time Frame
Any time after randomization up to 12 weeks.
Title
Number of Participants Who Discontinued Use of Treatment Due to Adverse Events
Description
Paticipants who dropped out of the study because of intolerable adverse events.
Time Frame
Any time after randomization up to 12 weeks.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Female and male outpatients between 18-65 years of age.
Meet criteria for revised Center for Disease Control (CDC) definition of Chronic Fatigue Syndrome (CFS) (at least 6 months of persistent fatigue that substantially reduces the person's level of activity; 4 or more of the following symptoms that must occur with fatigue in a 6-month period: impaired memory or concentration, sore throat, tender glands, aching or stiff muscles, multijoint pain, new headaches, unrefreshing sleep, and post-exertional fatigue. Medical conditions that may explain the fatigue and psychiatric disorders, including eating disorders, psychotic disorders, bipolar disorder, melancholic depression, and substance abuse within 2 years of the onset of fatigue, are excluded).
Provision of written informed consent for participation in the trial.
Educational level and degree of understanding such that the patient can communicate intelligibly with the investigator and study staff.
Judged to be reliable and agree to keep all appointments for clinic visits, tests, and procedures required by the protocol.
Exclusion Criteria:
Current melancholic major depressive disorder, or a previous diagnosis of psychosis, eating disorder, or bipolar disorder.
History of substance abuse or dependence within the past year, excluding nicotine and caffeine.
A positive urine drug screen for any substance of abuse (may be retested if positive test was for a prescribed medication that was not washed out).
Women who are pregnant or breast feeding; women must test negative for pregnancy at Visit 1.
Women of childbearing potential who are not using a medically accepted means of contraceptive when engaging in sexual intercourse.
Patients who, in the opinion of the investigator, are treatment-refractory or whose response is likely to be compromised by existing or future disability compensation issues.
Serious unstable medical illness, including cardiovascular, hepatic, renal, respiratory, or hematologic illness, or other unstable medical or psychiatric conditions that in the opinion of the investigator would compromise participation or would likely lead to hospitalization during the duration of the study. Abnormal thyroid stimulating hormone (TSH) concentrations (unless treatment for hypothyroidism has been stable for at least the past 3 months and the patient is clinically euthyroid).
Patients who have uncontrolled narrow-angle glaucoma.
Patients who have acute liver injury (such as hepatitis) or severe cirrhosis (Child-Pugh Class C).
Patients who are judged prior to randomization to be at suicidal risk by the clinical investigator.
Treatment with antidepressant medication within 14 days prior to randomization with the exception of fluoxetine, which cannot be used within 30 days prior to randomization. Potential need to use a monoamine oxidase inhibitor (MAOI) during the study or within 2 weeks of discontinuation of study treatment.
Patients who have previously taken duloxetine
Patients who are taking any excluded medications that cannot be discontinued at Visit 1.
Treatment within the last 30 days with a drug that has not received regulatory approval at the time of study entry.
Known hypersensitivity to duloxetine or any of the inactive ingredients.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lesley M Arnold, MD
Organizational Affiliation
University of Cincinnati Women's Health Research Program
Official's Role
Principal Investigator
Facility Information:
Facility Name
Women's Health Research Program
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
25660434
Citation
Arnold LM, Blom TJ, Welge JA, Mariutto E, Heller A. A randomized, placebo-controlled, double-blinded trial of duloxetine in the treatment of general fatigue in patients with chronic fatigue syndrome. Psychosomatics. 2015 May-Jun;56(3):242-53. doi: 10.1016/j.psym.2014.12.003. Epub 2014 Dec 16.
Results Reference
derived
Links:
URL
http://psychiatry.uc.edu/research/clinical/womenshealth.aspx
Description
Women's Health Research Program
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Double Blind Trial of Duloxetine in Chronic Fatigue Syndrome
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