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

NCT ID: NCT01318356

Last Updated: 2021-06-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 156 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-04-30
• Study Completion Date: 2015-09-30

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.

Conditions

Q Fever; Fatigue Syndrome, Chronic; Coxiella Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Cognitive behavioral therapy

Group Type: EXPERIMENTAL

Cognitive behavioral therapy

Intervention Type: BEHAVIORAL

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).

Doxycycline

Group Type: EXPERIMENTAL

Doxycycline

Intervention Type: DRUG

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.

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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)

Interventions

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).

Intervention Type: BEHAVIORAL

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.

Intervention Type: 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)

Intervention Type: DRUG

Other Intervention Names

Behavior Therapy, Cognitive; Cognition Therapy; Cognitive Behavior Therapy; Cognitive Psychotherapy; Psychotherapy, Cognitive; Therapy, Cognition; Therapy, Cognitive; Therapy, Cognitive Behavior; Doxycycline Monohydrate; Tetracycline; Sham Treatment

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ZonMw: The Netherlands Organisation for Health Research and Development

OTHER

Sponsor Role: collaborator

Radboud University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Stephan Keijmel

S.P. Keijmel, MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Chantal P Bleeker-Rovers, MD PhD

Role: STUDY_DIRECTOR

Radboud University Medical Center

Locations

Radboud university medical center

Nijmegen, Gelderland, Netherlands

Countries

Netherlands

References

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.

Reference Type: BACKGROUND

PMID: 23536997 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28329131 (View on PubMed)

Other Identifiers

2011-000643-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

205520003-20110307

Identifier Type: -

Identifier Source: org_study_id