Gulf War Illness Nasal Irrigation Study
Condition: Persian Gulf Syndrome; Chronic Sinusitis; Fatigue; Acute Sinusitis
MeSH terms: Sinusitis; Fatigue; Persian Gulf Syndrome
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Nasal Irrigation - Saline; Nasal Irrigation - Xylitol
Intervention type(s): Other; Drug
Intervention description(s): Liquid-based nasal irrigation (NI) is performed using a nasal irrigation cup ("neti pot"), a simple hand-held vessel that uses the force of gravity to gently irrigate the user's nasal cavity. Subjects will be requested to perform NI twice daily. The subjects will prepare the saline solution by themselves using the study-provided kit which will include packets of salt powder and the neti pot; subjects will dissolve the powder in lukewarm tap water to achieve a 2% buffered saline solution. The solution is then delivered to the nasal cavity using neti pot.; Liquid-based nasal irrigation (NI) is performed using a nasal irrigation cup ("neti pot"), a simple hand-held vessel that uses the force of gravity to gently irrigate the user's nasal cavity. Subjects will be requested to perform NI twice daily. The subjects will prepare the Xylitol solution by themselves using the study-provided kit which will include packets of Xylitol powder and the neti pot; subjects will dissolve the powder in lukewarm tap water to achieve a 5% Xylitol solution. The solution is then delivered to the nasal cavity using neti pot.
Other intervention name(s): 2% buffered saline; 5% Xylitol solution
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Gulf War Illness; xylitol; nasal irrigation; Desert Storm; Persian Gulf Conflicts; neti pot; cytokines; nasal mucus; inflammatory mediator; lactoferrin; lysozyme