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

June 22, 2021 updated by: Stephan Keijmel, Radboud University Medical Center
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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

156

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
    • Gelderland
      • Nijmegen, Gelderland, Netherlands, 6500 HB
        • Radboud University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • Sham 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:
  • Cognitive Behavior Therapy
  • Behavior Therapy, Cognitive
  • Cognition 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Checklist Individual Strength (CIS)
Time Frame: 24 weeks after start of treatment
The primary outcome measure is the fatigue severity measured by the subscale fatigue severity (8 items, 7-point Likert Scale) of the Checklist Individual Strength (CIS questionnaire) with a severity range from 8-56. High scores indicate a high level of fatigue. Patients with a cut-off score of ≥35 are classified as severely fatigued.
24 weeks after start of treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sickness Impact Profile (SIP) Total Score
Time Frame: 24 weeks after start of treatment
Level of functional impairment measured with the Sickness Impact Profile (SIP). The SIP is an instrument that is used to gauge sickness-related dysfunction. The weighted total score on eight subscales of the SIP8 (SIP8 total score) will be used to assess functional disability in all domains of functioning (range 0-5799). A higher score indicates higher levels of functional impairment. A score of 450 or higher on the SIP is defined as being significant disabled because of fatigue.
24 weeks after start of treatment
Symptom Checklist 90 (SCL90)
Time Frame: 24 weeks after start of treatment
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.
24 weeks after start of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Radboud University Medical Center

Collaborators

ZonMw: The Netherlands Organisation for Health Research and Development

Investigators

  • Study Director: Chantal P Bleeker-Rovers, MD PhD, Radboud University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2011

Primary Completion (ACTUAL)

September 1, 2015

Study Completion (ACTUAL)

September 1, 2015

Study Registration Dates

First Submitted

March 15, 2011

First Submitted That Met QC Criteria

March 17, 2011

First Posted (ESTIMATE)

March 18, 2011

Study Record Updates

Last Update Posted (ACTUAL)

June 23, 2021

Last Update Submitted That Met QC Criteria

June 22, 2021

Last Verified

June 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 205520003-20110307
  • 2011-000643-25 (EUDRACT_NUMBER)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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