Reactivation of CMV Infection in Immunocompetent Patients Under Severe Stress

NCT01397058 | Unknown DMC

• 1 other identifier: UAthens
• Study Type: observational
• Target: 275
• Locations: 1 country
• Sites: 1

Brief Summary

Background. Human herpes viruses establish lifelong latency after primary infection and may reactivate in immunosuppressed patients causing significant morbidity and mortality. In immunocompetent patients, although reactivation may occur disease development is deterred by the competent host immune response. Recent studies indicate that approximately one third of CMV seropositive immunocompetent ICU patients present with CMV reactivation associated with poor outcome, potentially secondary to the stress incurred. CMV reactivation among immunocompetent critically ill children has not been assessed. Study Hypothesis: Identifiable risk factors associated with CMV reactivation exist and may be used for future assessment of antiviral prophylaxis administration. Aim: Primary aim is to identify risk factors associated with CMV reactivation and poor outcome in immunocompetent children and adults under severe stress. Whether CMV reactivation occurs in critically ill children and its clinical implications remains to be determined. Secondary aim is to study the role of cellular signaling pathways of inflammation and specific adaptive immunity during this process. Work packages: A multicenter observational prospective study will be conducted among CMV seropositive pediatric and adult ICU patients. Patient clinical progress, laboratory findings, management, and complications will be recorded during the 28 days following ICU admission. Salivary free cortisol levels, plasma catecholamines, and serum cytokines levels will be measured to assess stress. CMV reactivation will be evaluated weekly by detecting CMV-DNA in peripheral blood and bronchial wash samples with real-time PCR. In a patient subsample, the nuclear factor κB and intracellular GC receptor will be measured in peripheral blood monocytes to study cellular signaling pathways of inflammation. The adaptive immune response to CMV infection following in vitro viral polypeptide stimulation will be prospectively examined in a subset of patients. Expected Results: The study will provide original data on critically ill children. Further knowledge regarding risk factors associated with CMV reactivation and poor outcome will be accumulated. Novel information regarding the role of cellular inflammation and specific adaptive immune responses during CMV reactivation will be gathered.

Conditions

Cytomegalovirus Viraemia; Stress, Physiological; Receptor, Hormonal; Disorder; Other Deficiency of Cell-mediated Immunity

Outcome Measures

Primary Outcomes (1)

• Risk factors associated with CMV reactivation in critically ill children and adults

  28 days

Secondary Outcomes (1)

• Role of cellular signaling and adaptive immunity

  7 days

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

ICU patients

You may qualify if:

• previously healthy children 5-16 years old (group A) and adults (group B)
• no known immunosuppression (secondary to underlying disease or medications),
• residence near the ICU (ability to return for follow up on day 28 post admission)
• availability of patient guardian or first degree relative willing to provide written informed consent

You may not qualify if:

• imminent death
• expected ICU stay \<48 hours
• intubation prior to admission (in a different center) for \>48 hours

Sponsors & Collaborators

• University of Athens: lead

Study Sites (1)

University of Athens

Athens, Greece

RECRUITING

Related Publications (1)

• Limaye AP, Kirby KA, Rubenfeld GD, Leisenring WM, Bulger EM, Neff MJ, Gibran NS, Huang ML, Santo Hayes TK, Corey L, Boeckh M. Cytomegalovirus reactivation in critically ill immunocompetent patients. JAMA. 2008 Jul 23;300(4):413-22. doi: 10.1001/jama.300.4.413.

  PMID: 18647984 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

As described above, whole blood will be collected on a weekly basis and DNA will be extracted to detect CMV-DNA. The remaining DNA will be retained

Study Officials

• Vassiliki Papaevangelou

  Univeristy of Athens , Greece

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vassiliki Papaevangelou

CONTACT

+30-2107793000; vpapaev@med.uoa.gr

Ioanna Dimopoulou

CONTACT

+30-2105832177; idimo@otenet.gr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: July 18, 2011
• First Posted: July 19, 2011
• Study Start: June 1, 2011
• Primary Completion: May 1, 2015
• Study Completion: June 1, 2015
• Last Updated: August 15, 2011

Record last verified: 2011-07

Locations

GR (1)