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CompletedNCT00375973CFSUpdated Aug 21, 2015Results posted

Double Blind Trial of Duloxetine in Chronic Fatigue Syndrome

A Phase 2/3 interventional study of Duloxetine and Placebo in Fatigue Syndrome, Chronic, sponsored by University of Cincinnati. Completed at 1 site in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2015-08-21.

Sponsored by University of Cincinnati · Phase 2/3, Interventional, and Treatment

Phase
Phase 2/3
Study type
Interventional
Enrollment
60
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study 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).

Read the 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.

02

Conditions studied

  • Fatigue Syndrome, Chronic

Keywords

  • Fatigue
  • Fatigue syndrome, chronic
  • Chronic fatigue syndrome
  • CFS
  • Fibromyalgia
03

In context

Fatigue Syndrome, Chronic

246 studies on the registry are indexed under Fatigue Syndrome, Chronic; 58 are open to participants now.

This study's enrollment of 60 is close to the median of 60 across 166 interventional studies indexed under Fatigue Syndrome, Chronic.

Browse Fatigue Syndrome, Chronic studies →

Lead sponsor

University of Cincinnati is the lead sponsor of 314 studies on the registry; 43 are open to participants now.

Of its 22 completed or terminated interventional studies of FDA-regulated products, 15 (68%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Female and male outpatients between 18-65 years of age.
  2. 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).
  3. Provision of written informed consent for participation in the trial.
  4. Educational level and degree of understanding such that the patient can communicate intelligibly with the investigator and study staff.
  5. Judged to be reliable and agree to keep all appointments for clinic visits, tests, and procedures required by the protocol.

Exclusion criteria

Exclusion Criteria:

  1. Current melancholic major depressive disorder, or a previous diagnosis of psychosis, eating disorder, or bipolar disorder.
  2. History of substance abuse or dependence within the past year, excluding nicotine and caffeine.
  3. 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).
  4. Women who are pregnant or breast feeding; women must test negative for pregnancy at Visit 1.
  5. Women of childbearing potential who are not using a medically accepted means of contraceptive when engaging in sexual intercourse.
  6. 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.
  7. 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).
  8. Patients who have uncontrolled narrow-angle glaucoma.
  9. Patients who have acute liver injury (such as hepatitis) or severe cirrhosis (Child-Pugh Class C).
  10. Patients who are judged prior to randomization to be at suicidal risk by the clinical investigator.
  11. 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.
  12. Patients who have previously taken duloxetine
  13. Patients who are taking any excluded medications that cannot be discontinued at Visit 1.
  14. Treatment within the last 30 days with a drug that has not received regulatory approval at the time of study entry.
  15. Known hypersensitivity to duloxetine or any of the inactive ingredients.
05

Study design

Phase
Phase 2 / Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Investigator, Outcomes assessor)
Enrollment
60 participants (actual)

Study arms

  • Experimental
    Duloxetine

    Duloxetine po 60-120 mg/day for 12 weeks

    Drug: Duloxetine

  • Placebo comparator
    Placebo

    Placebo comparator to Duloxetine

    Drug: Placebo

Interventions

  • DrugDuloxetine

    Duloxetine po 60-120 mg/day for 12 weeks

    Also known as: Cymbalta

  • DrugPlacebo

    Sugar pill dose comparable to duloxetine

    Also known as: Sugar Pill

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: Baseline to endpoint at 12 weeks

Secondary outcomes

  1. 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).

    Time frame: Baseline to endpoint at 12 weeks

  2. 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.

    Time frame: baseline to endpoint at 12 weeks

  3. 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.

    Time frame: baseline to endpoint at 12 weeks

  4. Patient Global Impression of Improvement (PGI-I)

    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.

  5. 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.

    Time frame: Any time after randomization up to 12 weeks.

  6. Number of Participants Who Discontinued Use of Treatment Due to Adverse Events

    Paticipants who dropped out of the study because of intolerable adverse events.

    Time frame: Any time after randomization up to 12 weeks.

07

Results

Posted Jul 27, 2015

Participant flow

Participant flow — Overall Study
MilestoneDuloxetinePlacebo
Started3030
Completed2028
Not completed102

Outcome measures

PrimaryChange 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.

Time frame:
Baseline to endpoint at 12 weeks
Reported as:
Mean · units on a scale
Change From Baseline in Multidimensional Fatigue Inventory (MFI)--General Fatigue Subscale Score
units on a scaleDuloxetinePlacebo
Change From Baseline in Multidimensional Fatigue Inventory (MFI)--General Fatigue Subscale Score-3.3 ± 4.2-1.8 ± 2.8
Statistical analysis
  • Duloxetine vs Placebo · Regression, Linear · p = 0.23
SecondaryChange 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).

Time frame:
Baseline to endpoint at 12 weeks
Reported as:
Mean · units on a scale
Change From Baseline in Brief Pain Inventory (BPI) --Average Pain Severity Score
units on a scaleDuloxetinePlacebo
Change From Baseline in Brief Pain Inventory (BPI) --Average Pain Severity Score-1.6 ± 1.5-0.8 ± 2.3
Statistical analysis
  • Duloxetine vs Placebo · Regression, Linear · p = 0.05
SecondaryChange 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.

Time frame:
baseline to endpoint at 12 weeks
Reported as:
Mean · units on a scale
Change From Baseline in the Hospital Anxiety and Depression Scale (HADS) --Depression Subscale
units on a scaleDuloxetinePlacebo
Change From Baseline in the Hospital Anxiety and Depression Scale (HADS) --Depression Subscale-1.6 ± 2.9-1.9 ± 3.0
Statistical analysis
  • Duloxetine vs Placebo · Regression, Linear · p = 0.67
SecondaryChange 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.

Time frame:
baseline to endpoint at 12 weeks
Reported as:
Mean · units on a scale
Change From Baseline in the Clinical Global Impression of Severity (CGI-S)
units on a scaleDuloxetinePlacebo
Change From Baseline in the Clinical Global Impression of Severity (CGI-S)-1.1 ± 1.2-0.4 ± 1.0
Statistical analysis
  • Duloxetine vs Placebo · Regression, Linear · p = 0.02
SecondaryPatient Global Impression of Improvement (PGI-I)

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.
Reported as:
Mean · units on a scale
Patient Global Impression of Improvement (PGI-I)
units on a scaleDuloxetinePlacebo
Patient Global Impression of Improvement (PGI-I)3.2 ± 1.23.3 ± 1.2
Statistical analysis
  • Duloxetine vs Placebo · Regression, Linear · p = 0.06
SecondaryNumber 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.

Time frame:
Any time after randomization up to 12 weeks.
Reported as:
Number · participants
Number of Participants Who Discontinued the Study for Any Reason
participantsDuloxetinePlacebo
Number of Participants Who Discontinued the Study for Any Reason102
Statistical analysis
  • Duloxetine vs Placebo · Fisher Exact · p = 0.02
SecondaryNumber of Participants Who Discontinued Use of Treatment Due to Adverse Events

Paticipants who dropped out of the study because of intolerable adverse events.

Time frame:
Any time after randomization up to 12 weeks.
Reported as:
Number · participants
Number of Participants Who Discontinued Use of Treatment Due to Adverse Events
participantsDuloxetinePlacebo
Number of Participants Who Discontinued Use of Treatment Due to Adverse Events30
Statistical analysis
  • Duloxetine vs Placebo · Fisher Exact · p = 0.24

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Duloxetine—1/29 (3.4%)29/29 (100%)
Placebo—0/30 (0%)30/30 (100%)
Most frequent serious events
Most frequent serious events
EventDuloxetinePlacebo
Suicidal ideationPsychiatric disorders1/290/30
Most frequent other events
Showing 10 of 29
Most frequent other events
EventDuloxetinePlacebo
NauseaGastrointestinal disorders19/296/30
SomnolenceNervous system disorders12/293/30
headacheNervous system disorders3/2912/30
InsomniaPsychiatric disorders10/294/30
dizzinessNervous system disorders9/292/30
ConstipationGastrointestinal disorders8/295/30
Cold virusInfections and infestations5/297/30
dry mouthGastrointestinal disorders6/291/30
Decreased appetiteGastrointestinal disorders5/291/30
DiarrheaGastrointestinal disorders5/293/30

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)DuloxetinePlaceboTotal
<=18 years000
Between 18 and 65 years303060
>=65 years000
Age, Continuous
Age, Continuous(years)DuloxetinePlaceboTotal
Mean43.0 ± 11.844.3 ± 11.043.6 ± 11.4
Sex: Female, Male
Sex: Female, Male(Participants)DuloxetinePlaceboTotal
Female262652
Male448
Region of Enrollment
Region of Enrollment(participants)DuloxetinePlaceboTotal
United States303060
08

Study locations

1 site
  • Women's Health Research Program
    Cincinnati, Ohio 45219, United States
09

References and documents

Publications

  • 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. PubMed 25660434 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 21, 2015, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00375973
Lead sponsor
University of Cincinnati
Collaborators
Eli Lilly and Company
Responsible party
Lesley M. Arnold, M.D. (Professor, University of Cincinnati) — Principal investigator
First posted
Sep 13, 2006
Start date
Sep 2006
Primary completion
Jun 2012
Completion
Mar 2014
Results posted
Jul 27, 2015
Last update
Aug 21, 2015

Study contacts

Lesley M Arnold, MD
principal investigator · University of Cincinnati Women's Health Research Program

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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