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The Qure Study: Q-fever Fatigue Syndrome - Response to Treatment (Qure)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01318356
Recruitment Status : Completed
First Posted : March 18, 2011
Last Update Posted : October 14, 2015
ZonMw: The Netherlands Organisation for Health Research and Development
Information provided by (Responsible Party):
Stephan Keijmel, Radboud University

Brief Summary:
The objective of this study is to assess the efficacy of two treatment strategies for fatigue and disabilities in QFS: long term treatment with doxycycline or cognitive behavioral therapy (CBT).

Condition or disease Intervention/treatment Phase
Q Fever Fatigue Syndrome, Chronic Coxiella Infection Behavioral: Cognitive behavioral therapy Drug: Doxycycline Drug: Placebo Phase 4

Detailed Description:

Q fever fatigue syndrome (QFS) is one of the most frequent sequelae of Q fever, and constitutes a significant problem in the current outbreak of Q fever. QFS leads to substantial morbidity and has a high socio-economic burden, related to increased use of healthcare facilities and absence from work. It is envisaged that over 750 patients will become chronically fatigued due to Q fever in The Netherlands (20% of 4000 patients from 2007 until now). Although the outbreak appears to diminish, it is expected that Q fever will remain an endemic disease, and therefore this number will continue to grow. A vast medical consumption can be anticipated, stressing the need for an accessible and effective intervention and clear treatment guidelines.

The study will contribute to a better understanding of effective treatment of QFS, providing evidence-based guidelines for general practitioners and medical specialists.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 156 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: The Qure Study: Q-fever Fatigue Syndrome - Response to Treatment
Study Start Date : April 2011
Actual Primary Completion Date : September 2015
Actual Study Completion Date : September 2015

Arm Intervention/treatment
Experimental: Cognitive behavioral therapy Behavioral: Cognitive behavioral therapy
CBT will consist of a protocolized intervention of 12 sessions during a period of 24 weeks. It starts with goal setting and psycho-education on the possible role of cognitions and behavior in maintaining the fatigue. The maintaining factors will subsequently be addressed (regulation of sleep-wake cycle, gradual increasing activity, reformulating fatigue related cognitions).
Other Names:
  • Behavior Therapy, Cognitive
  • Cognition Therapy
  • Cognitive Behavior Therapy
  • Cognitive Psychotherapy
  • Psychotherapy, Cognitive
  • Therapy, Cognition
  • Therapy, Cognitive
  • Therapy, Cognitive Behavior

Experimental: Doxycycline Drug: Doxycycline
Antibiotic therapy will consist of doxycycline once daily 200 mg (in 1 capsule) for 24 weeks. Patients will be monitored 4, 8, 16 and 26 weeks after start for side effects (rash, liver enzymes). Antibiotics will be stopped in case of side effects or pregnancy.
Other Names:
  • Doxycycline Monohydrate
  • Tetracycline

Placebo Comparator: Placebo Drug: Placebo
Patients in the placebo group will receive once daily 1 placebo capsule identical in appearance to the doxycycline for 24 weeks and have the same visits and monitoring for side effects as the patients randomized to doxycycline (Patients will be monitored 4, 8, 16 and 26 weeks)
Other Name: Sham Treatment

Primary Outcome Measures :
  1. Checklist Individual Strength (CIS) [ Time Frame: At baseline, after 8 weeks and after 24 weeks ]
    The Checklist Individual Strength measures the fatigue severity

Secondary Outcome Measures :
  1. Sickness Impact Profile (SIP) total score [ Time Frame: At baseline and after 24 weeks ]
    The Sickness Impact Profile measures the level of functional impairment

  2. Symptom Checklist 90 (SCL90) [ Time Frame: At baseline and after 24 weeks ]
    The total score of the Symptom Checklist 90 (SCL90) measures the level of psychological distress. The SCL90 consists of 90 items scored on a 5-point scale. Scores range from 90 to 450. A low total score reflects high psychological well-being. The SCL-90 is a reliable and valid instrument.

  3. Coxiella serology and PCR [ Time Frame: At baseline and after 26 weeks ]
    Serology consists of the antibodies IgG and IgM fase I and II and reflects the immunological respons to Coxiella burnetii of an individual subject. This will be compared to the antibody immunofluorescence titer measured at baseline.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Males or non-pregnant, non-lactating females who are 18 years or older
  • Laboratory-proven acute Q fever since the year 2007 and/or positive serology fitting a past infection with Coxiella burnetii;
  • AND being severely fatigued, defined by scoring 35 or higher on the subscale fatigue severity of the CIS;
  • AND being fatigued for at least 6 months;
  • AND disabled because of the fatigue, defined by scoring 450 or higher on the SIP
  • Subjects must sign a written informed consent form.

Exclusion Criteria:

  • Fulfilling criteria for chronic Q fever, namely:

    • IFA IgG fase I ≥ 1024, ≥ 3 months after acute Q fever and/or
    • Positive Coxiella burnetii PCR on serum or tissue, 1 month after acute Q fever
  • Acute Q fever in the setting of a prosthetic cardiac valve or aneurysm surgery or stenting necessitating prophylactic use of doxycycline;
  • Pregnancy or unwillingness to use effective contraceptives during the entire study period;
  • Imminent death;
  • Inability to give informed consent;
  • Allergy or intolerance to doxycycline;
  • Somatic or psychiatric illness that could explain the chronic fatigue;
  • Subjects who are currently enrolled on other investigational drug trials or receiving investigational agents;
  • Receiving antibiotics for more than 4 weeks, potentially active against Coxiella burnetii, for any other reason since Q-fever diagnosis;
  • Subjects who are receiving and cannot discontinue barbiturates, phenytoin, or carbamazepine (these drugs may increase the metabolism of doxycycline and therefore reducing half-life of doxycycline);
  • Moderate or severe liver disease (AF, ALAT, ASAT > 3 times the upper limit of normal).
  • Current engagement in a legal procedure concerning financial benefits (only current involvement interferes with the effectivity of cognitive behavioral therapy. Once the appeal procedure ends, subjects can be included)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01318356

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Radboud university medical center
Nijmegen, Gelderland, Netherlands, 6500 HB
Sponsors and Collaborators
Radboud University
ZonMw: The Netherlands Organisation for Health Research and Development
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Study Director: Chantal P Bleeker-Rovers, MD PhD Radboud University
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Stephan Keijmel, S.P. Keijmel, MD, Radboud University Identifier: NCT01318356    
Other Study ID Numbers: 205520003-20110307
2011-000643-25 ( EudraCT Number )
First Posted: March 18, 2011    Key Record Dates
Last Update Posted: October 14, 2015
Last Verified: October 2015
Keywords provided by Stephan Keijmel, Radboud University:
Q fever
Cognitive behavioral therapy
Additional relevant MeSH terms:
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Q Fever
Fatigue Syndrome, Chronic
Pathologic Processes
Body Temperature Changes
Gram-Negative Bacterial Infections
Bacterial Infections
Virus Diseases
Muscular Diseases
Musculoskeletal Diseases
Central Nervous System Diseases
Nervous System Diseases
Neuromuscular Diseases
Anti-Bacterial Agents
Anti-Infective Agents
Antiprotozoal Agents
Antiparasitic Agents
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action