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

Primary Purpose

Q Fever, Fatigue Syndrome, Chronic, Coxiella Infection

Status
Completed
Phase
Phase 4
Locations
Netherlands
Study Type
Interventional
Intervention
Cognitive behavioral therapy
Doxycycline
Placebo
Sponsored by
Radboud University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Q Fever focused on measuring Q fever, Cognitive behavioral therapy, Doxycycline, Fatigue, Coxiella

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Radboud university medical center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

Cognitive behavioral therapy

Doxycycline

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Checklist Individual Strength (CIS)
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.

Secondary Outcome Measures

Sickness Impact Profile (SIP) Total Score
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.
Symptom Checklist 90 (SCL90)
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.

Full Information

First Posted
March 15, 2011
Last Updated
June 22, 2021
Sponsor
Radboud University Medical Center
Collaborators
ZonMw: The Netherlands Organisation for Health Research and Development
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1. Study Identification

Unique Protocol Identification Number
NCT01318356
Brief Title
The Qure Study: Q-fever Fatigue Syndrome - Response to Treatment
Acronym
Qure
Official Title
The Qure Study: Q-fever Fatigue Syndrome - Response to Treatment
Study Type
Interventional

2. Study Status

Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
April 2011 (undefined)
Primary Completion Date
September 2015 (Actual)
Study Completion Date
September 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Radboud University Medical Center
Collaborators
ZonMw: The Netherlands Organisation for Health Research and Development

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Q Fever, Fatigue Syndrome, Chronic, Coxiella Infection
Keywords
Q fever, Cognitive behavioral therapy, Doxycycline, Fatigue, Coxiella

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
156 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cognitive behavioral therapy
Arm Type
Experimental
Arm Title
Doxycycline
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Behavioral
Intervention Name(s)
Cognitive behavioral therapy
Other Intervention Name(s)
Behavior Therapy, Cognitive, Cognition Therapy, Cognitive Behavior Therapy, Cognitive Psychotherapy, Psychotherapy, Cognitive, Therapy, Cognition, Therapy, Cognitive, Therapy, Cognitive Behavior
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
Doxycycline
Other Intervention Name(s)
Doxycycline Monohydrate, Tetracycline
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Sham Treatment
Intervention Description
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)
Primary Outcome Measure Information:
Title
Checklist Individual Strength (CIS)
Description
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.
Time Frame
24 weeks after start of treatment
Secondary Outcome Measure Information:
Title
Sickness Impact Profile (SIP) Total Score
Description
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.
Time Frame
24 weeks after start of treatment
Title
Symptom Checklist 90 (SCL90)
Description
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.
Time Frame
24 weeks after start of treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chantal P Bleeker-Rovers, MD PhD
Organizational Affiliation
Radboud University Medical Center
Official's Role
Study Director
Facility Information:
Facility Name
Radboud university medical center
City
Nijmegen
State/Province
Gelderland
ZIP/Postal Code
6500 HB
Country
Netherlands

12. IPD Sharing Statement

Citations:
PubMed Identifier
23536997
Citation
Keijmel SP, Delsing CE, Sprong T, Bleijenberg G, van der Meer JW, Knoop H, Bleeker-Rovers CP. The Qure study: Q fever fatigue syndrome--response to treatment; a randomized placebo-controlled trial. BMC Infect Dis. 2013 Mar 27;13:157. doi: 10.1186/1471-2334-13-157.
Results Reference
background
PubMed Identifier
28329131
Citation
Keijmel SP, Delsing CE, Bleijenberg G, van der Meer JWM, Donders RT, Leclercq M, Kampschreur LM, van den Berg M, Sprong T, Nabuurs-Franssen MH, Knoop H, Bleeker-Rovers CP. Effectiveness of Long-term Doxycycline Treatment and Cognitive-Behavioral Therapy on Fatigue Severity in Patients with Q Fever Fatigue Syndrome (Qure Study): A Randomized Controlled Trial. Clin Infect Dis. 2017 Apr 15;64(8):998-1005. doi: 10.1093/cid/cix013.
Results Reference
derived

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

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