From BMC Infectious Diseases, 27 March 2013.
The Qure study: Q fever fatigue syndrome – response to treatment; a randomized placebo-controlled trial
Stephan P Keijmel(1,2,3,7,*), Corine E Delsing(4), Tom Sprong(1,2,3,5), Gijs Bleijenberg(6), Jos WM van der Meer(1,2,3), Hans, A Knoop(6), Chantal P Bleeker-Rovers(1,2,3)
1 Radboud Expertise Centre for Q fever, Department of InternalMedicine, Division of Infectious Diseases, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500, HB Nijmegen, the Netherlands
2 Department of Internal Medicine and division of Infectious Diseases, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500, HB Nijmegen, the Netherlands
3 Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500, HB Nijmegen, the Netherlands
4 Department of Internal Medicine, Medical Spectrum Twente, P.O. Box 50000, 7500, KA Enschede, the Netherlands
5 Department of Internal Medicine and division of Infectious Diseases, Canisius Wilhelmina Hospital, P.O. Box 9015, 6500, GS Nijmegen, the Netherlands
6 Expert Centre for Chronic Fatigue, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500, HB Nijmegen, the Netherlands
7 Department of Internal Medicine/Division of Infectious Diseases 463, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500, HB Nijmegen, The Netherlands
* Corresponding author. Department of Internal Medicine/Division of Infectious Diseases 463, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500, HB Nijmegen, The Netherlands Email: s.keijmel@aig.umcn.nl
Abstract
BACKGROUND
Q fever is a zoonosis that is present in many countries. Q fever fatigue syndrome (QFS) is one of the most frequent sequelae after an acute Q fever infection. QFS is characterized by persistent fatigue following an acute Q fever infection, leading to substantial morbidity and a high socio-economic burden. The occurrence of QFS is well-documented, and has been described in many countries over the past decades. However, a treatment with proven efficacy is not available. Only a few uncontrolled studies have tested the efficacy of treatment with antibiotics on QFS. These studies suggest a positive effect of long-term treatment with a tetracycline on performance state; however, no randomized controlled trials have been performed. Cognitive behavioral therapy (CBT) has been proven to be an effective treatment modality for chronic fatigue in other diseases, but has not yet been tested in QFS. Therefore, we designed a trial to assess the efficacy of long-term treatment with the tetracycline doxycycline and CBT in patients with QFS.
METHODS/DESIGN
A randomized placebo-controlled trial will be conducted. One-hundred-eighty adult patients diagnosed with QFS will be recruited and randomized between one of three groups: CBT, long-term doxycycline or placebo. First, participants will be randomized between CBT and medication (ratio 1:2). A second double-blinded randomization between doxycycline and placebo (ratio 1:1) will be performed in the medication condition. Each group will be treated for six months. Outcome measures will be assessed at baseline and post intervention. The primary outcome measure is fatigue severity. Secondary outcome measures are functional impairment, level of psychological distress, and Coxiella burnetii PCR and serology.
DISCUSSION
The Qure study is the first randomized placebo-controlled trial, which evaluates the efficacy of long-term doxycycline and of cognitive behavioral therapy in patients with QFS. The results of this study will provide knowledge about evidence-based treatment options for adult patients with QFS.Trial registration: ClinicalTrials.gov: NCT01318356, and Netherlands Trial Register: NTR2797
From Molecular and Cellular Endocrinoogy, 26 March 2013 [Epub ahead of print].
Continuous stress promotes expression of VGF in melanotroph via suppression of dopamine.
Tokizane K(a), Konishi H(a), Yasui M(a), Ogawa T©, Sasaki K(b), Minamino N(b), Kiyama H(a).
(a)Department of Functional Anatomy and Neuroscience, Nagoya University, Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
(b) Department of Molecular Pharmacology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka 565-8565, Japan
Abstract
Prolonged exposure to stress elicits profound effects on homeostasis that may lead to cryptogenic disorders such as chronic fatigue syndrome.
To investigate the pathophysiology associated with the syndrome, we used a rat continuous stress (CS) model where the pituitary represents one of the most affected organs. Here we found that mRNA for VGF (non-acronymic), a member of the granin family, was induced specifically in the intermediate lobe (IL).
This was matched by a concomitant increase at the peptide/protein level assessed by C-terminal antibody. Furthermore, the upregulation of VGF was confirmed by immunohistochemistry in a subset of melanotrophs.
VGF expression was altered in the IL of rats receivingthe dopamine D2receptor agonist bromocriptine or the antagonist sulpiride. In vitro, dopamine dose dependently decreased the mRNA levels in cultured melanotrophs.
These findings suggest that VGF expression under CS is negatively regulated by dopaminergic neurons projecting from the hypothalamus.