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

NCT01318356 | Completed Phase 4 Results DMC

• 2 other identifiers: 205520003-201103072011-000643-25
• Study Type: interventional
• Target: 156
• Locations: 1 country
• Sites: 1

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).

Conditions

Q Fever; Fatigue Syndrome, Chronic; Coxiella Infection

Keywords

Q fever; Cognitive behavioral therapy; Doxycycline; Fatigue; Coxiella

Outcome Measures

Primary Outcomes (1)

• 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.

  24 weeks after start of treatment

Secondary Outcomes (2)

• Sickness Impact Profile (SIP) Total Score

  24 weeks after start of treatment

• Symptom Checklist 90 (SCL90)

  24 weeks after start of treatment

Study Arms (3)

Cognitive behavioral therapy

EXPERIMENTAL

Behavioral: Cognitive behavioral therapy

Doxycycline

EXPERIMENTAL

Drug: Doxycycline

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Cognitive behavioral therapy 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).

Also known as: Behavior Therapy, Cognitive, Cognition Therapy, Cognitive Behavior Therapy, Cognitive Psychotherapy, Psychotherapy, Cognitive, Therapy, Cognition, Therapy, Cognitive, Therapy, Cognitive Behavior

Cognitive behavioral therapy

Doxycycline 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.

Also known as: Doxycycline Monohydrate, Tetracycline

Doxycycline

Placebo 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)

Also known as: Sham Treatment

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Radboud University Medical Center: lead
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator

Study Sites (1)

Radboud university medical center

Nijmegen, Gelderland, 6500 HB, Netherlands

Location

Related Publications (2)

• 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.

  PMID: 23536997 BACKGROUND

• 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.

  PMID: 28329131 DERIVED

MeSH Terms

Conditions

Q Fever; Fatigue Syndrome, Chronic; Fatigue

Interventions

Cognitive Behavioral Therapy; Doxycycline; Tetracycline

Condition Hierarchy (Ancestors)

Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Muscular Diseases; Musculoskeletal Diseases; Encephalomyelitis; Neuroinflammatory Diseases; Nervous System Diseases; Neuromuscular Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities; Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Limitations and Caveats

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.

Results Point of Contact

• Title: S.P. Keijmel, MD PhD
• Organization: Radboud university medical center

stephan.keijmel@radboudumc.nl

0031243611111

Study Officials

• Chantal P Bleeker-Rovers, MD PhD

  Radboud University Medical Center

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: S.P. Keijmel, MD

Study Record Dates

• First Submitted: March 15, 2011
• First Posted: March 18, 2011
• Study Start: April 1, 2011
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: June 23, 2021
• Results First Posted: June 23, 2021

Record last verified: 2021-06

Locations

NL (1)