Double Blind Trial of Duloxetine in Chronic Fatigue Syndrome (CFS)

A Randomized, Placebo-Controlled, Double-Blind Trial of Duloxetine in the Treatment of Patients With Chronic Fatigue Syndrome

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).

Study Overview

• Status: Completed
• Conditions: Fatigue Syndrome, Chronic
• Intervention / Treatment: Drug: Duloxetine; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Duloxetine; Duloxetine po 60-120 mg/day for 12 weeks	Drug: Duloxetine; Duloxetine po 60-120 mg/day for 12 weeks; Other Names: Cymbalta
Placebo Comparator: Placebo; Placebo comparator to Duloxetine	Drug: Placebo; Sugar pill dose comparable to duloxetine; Other Names: Sugar Pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline to endpoint at 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Baseline to endpoint at 12 weeks
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.	baseline to endpoint at 12 weeks
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.	baseline to endpoint at 12 weeks
Patient Global Impression of Improvement (PGI-I)	Patient rated assessment of change on a 1 (very much better) to 7 (very much worse) scale.	baseline to endpoint at 12 weeks.
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.	Any time after randomization up to 12 weeks.
Number of Participants Who Discontinued Use of Treatment Due to Adverse Events	Paticipants who dropped out of the study because of intolerable adverse events.	Any time after randomization up to 12 weeks.

Collaborators and Investigators

• Sponsor: University of Cincinnati
• Collaborators: Eli Lilly and Company
• Investigators: Principal Investigator: Lesley M Arnold, MD, University of Cincinnati Women's Health Research Program

Publications and helpful links

General 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.

Helpful Links

• Women's Health Research Program

Study record dates

Study Major Dates

• Study Start: September 1, 2006
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: September 12, 2006
• First Submitted That Met QC Criteria: September 12, 2006
• First Posted (Estimate): September 13, 2006

Study Record Updates

• Last Update Posted (Estimate): August 21, 2015
• Last Update Submitted That Met QC Criteria: July 31, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: Fatigue; CFS; Fibromyalgia; Chronic fatigue syndrome; Fatigue syndrome, chronic
• Additional Relevant MeSH Terms: Pathologic Processes; Central Nervous System Diseases; Nervous System Diseases; Virus Diseases; Infections; Disease; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Encephalomyelitis; Syndrome; Fatigue; Fatigue Syndrome, Chronic; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Dopamine Agents; Serotonin and Noradrenaline Reuptake Inhibitors; Duloxetine Hydrochloride
• Other Study ID Numbers: 06-05-01-02