Clinical trial NCT01700725: Gulf War Illness Nasal Irrigation Study
Official title: Nasal Irrigation for Chronic Rhinosinusitis and Fatigue in Patients With Gulf War Illness
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Persian Gulf Syndrome
Chronic Sinusitis
Fatigue
Acute Sinusitis
Keywords: Gulf War Illness
xylitol
nasal irrigation
Desert Storm
Persian Gulf Conflicts
neti pot
cytokines
nasal mucus
inflammatory mediator
lactoferrin
lysozyme
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
First posted: 2012-10-04
Enrollment: 40
Sex: ALL
Minimum age (years): 35
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether nasal irrigation with Xylitol or saline are effective in the treatment of chronic rhinosinusitis and fatigue symptoms associated with Gulf War Illness.

Detailed description: Background: Gulf War Illness (GWI) results in tremendous impact to quality of life. Symptoms of chronic rhinosinusitis (CRS) and fatigue are the first (47%) and third (41%) most common symptoms of patients with GWI, respectively. These symptoms are biologically characterized by a milieu of elevated levels of proinflammatory cytokines; to date, the profile of these cytokines in serum and nasal secretions is incompletely understood and has not been assessed in response to therapy. Nasal irrigation (NI) is a therapy which bathes the nasal cavity with a solution (liquid). There are two promising forms of NI; saline NI (S-NI) is hypothesized to improve sinus symptoms by thinning and clearing mucus and inflammatory mediators, decreasing mucosal edema and improving ciliary function. Xylitol NI (X-NI) has been shown to change the salinity of the mucosal surface resulting in enhanced antimicrobial properties. Although NI is an evidence-based adjunctive therapy for CRS and has been reported to be effective for CRS and fatigue, it has not been assessed in a GWI population.

Specific Aims, Hypotheses and Study Design: The specific aims of this proposal are to determine whether routine care plus S-NI, or X-NI, compared to routine care alone, result in improved health-related quality of life (HRQoL), are cost-effective and decrease proinflammatory bias in subjects with GWI who suffer from CRS and fatigue.

Consistent with our specific aims, we will test the following hypotheses: In an RCT setting, at 26 weeks post-enrollment, adults with GWI and symptoms of CRI and fatigue, treated with routine care plus S-NI or X-NI, compared to those treated with routine care alone, will demonstrate:

H1: improved HRQoL: a) sinus-disease specific HRQoL as evaluated by the validated Sinonasal Outcomes Test (SNOT-20) questionnaire (primary outcome measure); b) fatigue-specific HRQoL as assessed by the validated questionnaire, the Multidimensional Fatigue Inventory (MFI); and c) overall HRQoL as assessed by the validated questionnaire the Medical Outcomes Survey Short Form-36 (SF-36; mental and physical health domains) augmented with 18 sleep- and breathing related questions.

H.2: greater cost-effectiveness as measured by the average cost of the intervention divided by the average effectiveness (as assessed by a improvement in SNOT-20 scores), and reported as the "dollars spent per subject restored to health."

H.3: improved treatment satisfaction as assessed by a single-item treatment satisfaction score and a qualitative exit interview.

H.4: improved proinflammatory bias: a) reduced activation and dysregulation of proinflammatory pathways as determined by a reduction in URI-specific inflammatory cytokines in serum and nasal secretions; and b) improved serum-based complete blood count, sedimentation rate or C-reactive protein, or nasal swab-based neutrophil or eosinophil counts.

Study Design: 26 week duration of follow-up, 3-arm RCT (N=75). All groups will utilize routine care for their GWI and symptoms of CRS and fatigue. Groups 1 and 2 will in addition add S-NI or X-NI twice daily to their routine care, respectively. Group 3 will continue to use routine care with no other additions (control group); control group participants will be offered NI training and related materials (xylitol or saline per subject preference) after they complete their 26-week follow-up period.

Impact: Positive findings would suggest a number of important effects:

* Statistically positive results on HRQoL outcome measures would suggest that NI can provide effective adjunctive therapy for CRS and fatigue in adults with GWI, improving health of affected patients and potentially providing gains to society through reduced health care utilization and absenteeism related costs.
* Positive biomarker findings would contribute to our better understanding of the etiology of CRS and fatigue in the GWI population and of possible biological pathways underlying the NI efficacy.
* The finding that either form of NI is cost effective would provide economic justification for its clinical use.

Eligibility criteria: Inclusion Criteria:

* English fluency and basic reading and writing literacy.
* Deployment to the Persian Gulf (e.g., Iraq, Kuwait, Saudi Arabia) for the purpose of Operation Desert Shield or Operation Desert Storm during the first Gulf War (1990-1991).
* Meeting criteria for a diagnosis of GWI as based on the "Kansas" GWI case definition; only the Kansas case definition (from among the several currently used case definitions) can differentiate between Gulf War-deployed and non-deployed Gulf era veterans.
* Meeting criteria for a diagnosis of chronic rhinosinusitis (CRS) using self-reported symptoms and based on clinical guidelines; eligible subjects will report: • sinonasal symptoms for at least 12 weeks; • a constellation of sinonasal symptoms including either two or more major factors, or 1 major and 2 minor factors (see Table 1 below), or chronic nasal purulence for 12 or more weeks; and • a moderate to severe HRQoL impact (≥ 3 points on a 0-10 Likert severity scale) as assessed by a single item question:11 "What has been the average level of your sinus symptoms daily over the past month on a 0-10 scale?" This item is consistent with eligibility criteria used in prior NI studies.
* Chronic fatigue of moderate-to-severe severity defined as scoring at least 3 points on a single question (0-10 Likert scale): "What has been the average level of your daily fatigue over the past month on a 0-10 scale?"

Exclusion Criteria:

* Self-reported pregnancy.
* Current use of liquid NI or xylitol nasal spray; regular use is defined as 1 or more irrigations weekly for 3 consecutive weeks.
* Self-reported neurological or musculoskeletal conditions that could facilitate aspiration, or patients who otherwise cannot physically perform the NI procedure.
* Self-reported borderline personality disorder.
* Inability or stated reluctance to reliably participate in study activities.
* Severe or unstable mental health problems that would preclude safe or reliable study participation as based on an in-person evaluation by a psychiatry team; active delusional disorder, depressive disorder or alcohol/drug abuse or dependence will be a primary target of this interview using both a structured clinical interview (MINI ref) and psychiatry team evaluation.

Primary outcomes:
measure: Change in Sino-Nasal Outcome Test (SNOT-20) Score From Baseline
timeFrame: Change from baseline week 8, change from baseline week 26
Secondary outcomes:
measure: Change in Multidimensional Fatigue Inventory (MFI) Over Baseline
timeFrame: Baseline to weeks 8 & 26
measure: Change in Medical Outcomes Survey Short Form-36 (SF-36) Over Baseline
timeFrame: Baseline and weeks 8 & 26
Other outcomes:
Locations:
city: Madison
country: United States
facility: University of Wisconsin General Clinical Research Center
state: Wisconsin
Study officials:
affiliation: US Department of Veterans Affairs, William S. Middleton Memorial Veterans Hospital
name: Rachel Molander, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Wisconsin, Madison
name: David P Rabago, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hayer SD, Rabago DP, Amaza IP, Kille T, Coe CL, Zgierska A, Zakletskaia L, Mundt MP, Krahn D, Obasi CN, Molander RC. Effectiveness of nasal irrigation for chronic rhinosinusitis and fatigue in patients with Gulf War illness: protocol for a randomized controlled trial. Contemp Clin Trials. 2015 Mar;41:219-26. doi: 10.1016/j.cct.2015.01.008. Epub 2015 Jan 24.