Q FeverPhase 4QureNCT01318356

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

A Phase 4 study testing Cognitive behavioral therapy and Doxycycline in people with Q Fever and Fatigue Syndrome, Chronic, run by Radboud University Medical Center at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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). Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Q Fever, Fatigue Syndrome, Chronic, Coxiella Infection
What is being tested?: Cognitive behavioral therapy and Doxycycline
Type of treatment: Pill or oral medicine, Lifestyle or therapy programme
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 156 participants
Where: 1 siteNetherlands
Study dates: Apr 2011to Sep 2015
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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;

Show all 14Show fewer

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)

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

Radboud university medical center
Nijmegen, Gelderland, 6500 HB

Other trials in Netherlands

About this study

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).

Read the 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.

Conditions: Q Fever, Fatigue Syndrome, Chronic, Coxiella Infection
Being tested: Cognitive behavioral therapy, Doxycycline, Placebo
Keywords: Q fever, Cognitive behavioral therapy, Doxycycline, Fatigue, Coxiella
Medical subject headings: Q Fever, Fatigue Syndrome, Chronic, Fatigue

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Cognitive behavioral therapyBehavioural
Also called Behavior Therapy, Cognitive, Cognition Therapy, Cognitive Behavior Therapy, Cognitive Psychotherapy
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).
DoxycyclineDrug
Also called Doxycycline Monohydrate, Tetracycline
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.
PlaceboDrug
Also called Sham Treatment
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)

Study groups in NCT01318356
Study group	Role	What they receive
Cognitive behavioral therapy	Experimental	Not described Receives: Behavioral: Cognitive behavioral therapy
Doxycycline	Experimental	Not described Receives: Drug: Doxycycline
Placebo	Placebo comparator	Not described Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 24 weeks after start of treatment

Secondary outcomes (2)

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.
Measured: 24 weeks after start of treatment
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.
Measured: 24 weeks after start of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Apr 2011Sep 2015

First posted18 Mar 2011 (estimated)
Study startApr 2011
Primary completionSep 2015
Study completionSep 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Q FeverStudies of the same condition, open and under way.
More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 156 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01318356
Sponsor's protocol ID: 205520003-20110307
Other IDs: 2011-000643-25
Acronym: Qure
Status last verified: Jun 2021
First submitted: 15 Mar 2011
Last updated: 23 Jun 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

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.
PubMed 23536997
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.
PubMed 28329131

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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All Q Fever trials

Study at a glance

From the registry record, last updated by the sponsor on 23 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: The Qure Study: Q-fever Fatigue Syndrome - Response to Treatment
ClinicalTrials.gov ID: NCT01318356
Acronym / sponsor ID: Qure / 205520003-20110307
Conditions: Q Fever, Fatigue Syndrome, Chronic, Coxiella Infection
Keywords: Q fever, Cognitive behavioral therapy, Doxycycline, Fatigue, Coxiella
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 156 participants (actual)
Lead sponsor: Radboud University Medical CenterUniversity, hospital or other
Collaborators: ZonMw: The Netherlands Organisation for Health Research and Development
Study start: Apr 2011
Primary completion: Sep 2015 (actual)
Study completion: Sep 2015 (actual)
First posted: 18 Mar 2011 (estimated)
Results: Posted 23 Jun 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 3

Arm	Type	Receives
Cognitive behavioral therapy	Experimental	Behavioral: Cognitive behavioral therapy
Doxycycline	Experimental	Drug: Doxycycline
Placebo	Placebo comparator	Drug: Placebo

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

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

Key exclusion criteria (14 listed)

Fulfilling criteria for chronic Q fever, namely:
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;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Cognitive behavioral therapyAlso: Behavior Therapy, Cognitive, Cognition Therapy, Cognitive Behavior Therapy, Cognitive PsychotherapyCBT 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).	Behavioural	Cognitive behavioral therapy
DoxycyclineAlso: Doxycycline Monohydrate, TetracyclineAntibiotic 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.	Drug	Doxycycline
PlaceboAlso: Sham TreatmentPatients 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)	Drug	Placebo

Primary outcome

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.

2 secondary outcomes

Sickness Impact Profile (SIP) Total Score
Time frame: 24 weeks after start of treatment
Symptom Checklist 90 (SCL90)
Time frame: 24 weeks after start of treatment

Results and safety

Results posted to the registry on 23 Jun 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cognitive Behavioral Therapy	51	43
Doxycycline	52	49
Placebo	52	50

Primary outcome: Checklist Individual Strength (CIS)

Time frame: 24 weeks after start of treatment. Mean (95% Confidence Interval). Unit: score on a scale

Measure	Cognitive Behavioral Therapy n = 50	Doxycycline n = 52	Placebo n = 52
Value	31.6 (28.0 to 35.1)	40.8 (37.3 to 44.3)	37.8 (34.3 to 41.2)

Population analysed: Intention-to-treat analysis

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Safety was assessed by monitoring adverse events (AEs) and concomitant drug use. For patients allocated to the medication condition, AEs were monitored at 4 weeks, 8 weeks, and 16 weeks after start of therapy, and at EOT (= up to approximately 26 weeks after start of therapy). Furthormore, if applicable, during the trial when reported by the patient. For patients allocated to CBT, AEs were monitored at 8 weeks after start of therapy, and at EOT (up to 26 weeks after start of therapy).. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cognitive Behavioral Therapy	0 of 50 (0%)	42 of 50 (84%)	0 of 50
Doxycycline	0 of 52 (0%)	51 of 52 (98.1%)	0 of 52
Placebo	2 of 52 (3.8%)	45 of 52 (86.5%)	0 of 52

Limitations and caveats (from the sponsor): It was not designed to compare doxycycline and CBT directly, due to the limited number of available patients. As masking for CBT was not possible, this trial was partly blinded. CBT was directly compared to placebo plus usual care. Due to the maximum number of vailable patients, it was not possible to include a control group without any form of treatment. Finally, it is unclear whether the detected effects will be sustained over time.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 23536997Keijmel 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.
Derived from this study: PubMed 28329131Keijmel 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Chantal P Bleeker-Rovers, MD PhD study director

Radboud University Medical Center

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Cognitive behavioral therapy and Doxycycline in people with Q Fever and Fatigue Syndrome, Chronic, run by Radboud University Medical Center at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Checklist Individual Strength (CIS) (time frame: 24 weeks after start of treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01318356, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jun 2021.