Hyperbaric Oxygen Therapy for Inflammatory Conditions of the Urinary Bladder
Hyperbaric Oxygen Therapy for Inflammatory Conditions of the Urinary Bladder
Pilot study to determine feasibility for treating patients with two chronic inflammatory
 conditions of the urinary bladder: chronic interstitial cystitis and recurrent urinary tract
 infections using a standardized hyperbaric oxygen treatment plan. Presently there are no good
 treatments for these conditions and hyperbaric oxygen may be a safe and readily accessible
 therapy as it has proven successful an another type of chronic inflammatory condition of the
 urinary bladder known as "radiation cystitis". The study will determine if patients will
 consider this an acceptable treatment for their conditions and that it is well tolerated.
The primary object is to determine the feasibility of treating patients diagnosed with either
 CIC/PBS or rUTI with daily hyperbaric oxygen for a total of 40 treatment sessions during an
 8-10 week time period. We wish to better understand the demand and degree of adherence for
 daily HBOT in these two patient populations to inform future planning and design of
 randomized, sham controlled and double-blind studies. Given the refractory nature of these
 two diagnoses, a secondary objective of this study is to determine if there is symptomatic
 improvement following HBOT compared to pretreatment symptoms using standardized patient
 symptomology questionnaires' (Global Response Assessment-GRA and Patient's Overall Rating of
 Improvement in Symptoms-PORIS questionnaires).

 Patient selection will be carried out by the respective co-investigators based on standard
 disease definitions. CIC/PBS is defined as urinary tract pain or discomfort and dysuria that
 is present of > 6 months and is not due to acute urinary tract infection, stones or other
 pathology. These patients will be identified and recruited by Dr. C. Lowell Parsons,
 Co-investigator for the study. rUTI is defined as greater than 2 urinary tract infections in
 6 month or greater than 3 urinary tract infections in one year. These patient will be
 identified and recruited by Dr. Emily Lukacz, Co-investigator. Each study will enroll 20
 individuals. The study design is an observational pilot study to determine feasibility and
 limited efficacy. Thus the primary outcomes will be the number of patients that enroll in the
 study relative to the number offered enrollment and the percentage of individuals completing
 the prescribed 40 treatment sessions. For the secondary outcome, limited efficacy, each
 patient's pre-treatment clinical status will be compared to their post treatment clinical
 status. Thus for the CIC/PBS study both the global response assessment (GRA) and the
 patient's overall rating of improvement of symptoms (PORIS) will be obtained and comparison
 between the pre and post treatment scores will be performed. For the UTI study, the time in
 days to subsequent acute urinary tract infection and total number of acute UTI's during one
 year following completion of HBOT will be recorded and compared to that individual's prior
 clinical history. The dosing algorithm to be used is based on the current standard of care
 for the treatment of radiation cystitis for which 2.4 ATA x 90 minutes is provided daily, 5
 days per week. The total duration of treatment can range from 30-60 minutes depending upon
 the individual patients severity of illness and response to therapy. Patients are routinely
 reassessed after every 10-20 treatments. Therefore we are planning to provide 2.4 ATA x 90
 minutes with 2 air breaks daily, x 5 days per week x 8 weeks total for both CIC/PBS and rUTI
 patient population. We will allow the 40 treatments to be administered over an 8-10 week time
 period to provide some degree of scheduling flexibility for patients.

 For this feasibility study we will determine the demand as measured by the number of patients
 accepting the treatment vs the total number of patients offered enrollment. We will determine
 the percentage successful completion of the 40 prescribed treatment sessions as the primary
 outcome variable. The results of the symptom questionnaires obtained at the conclusion for
 HBOT and by follow up telephone survey at 1, 6 and 12 months following completion of HBOT
 will be the secondary outcome variable. Finally, adverse events will be gathered on this
 patient population as per routine clinical practice. The incidence and severity of otic
 barotrauma, hyperoxic myopia, confinement anxiety and generalized seizures will be determined
 and compared to the same events experienced by the general hyperbaric patient population
 being treated during the same period of time.

 Symptom Survey Instruments Global Response Assessment (GRA) The GRA measures overall
 improvement with therapy. It is now used as the primary end point in clinical trials of
 therapies for CIC/PBS. The assessment asks: "As compared to when you started the study
 [treatment], how would you rate your interstitial cystitis symptoms now?" The seven point
 scale is centered at zero (no change): markedly worse; moderately worse; slightly worse; no
 change; slightly improved; moderately improved; and markedly improved. Responders will be
 defined as those individuals with scores falling in the moderately and markedly improved
 categories.

 Patient's Overall Rating of Improvement of Symptoms (PORIS) The PORIS has three questions
 that address the overall change in CIC/PBS, pain, and urgency after treatment as worse, no
 better (0% improvement), slightly improved (25%), moderately improved (50%), greatly improved
 (75%), or symptoms gone (100% improvement). Responders will be defined as those individuals
 with scores falling into the moderately or greatly improved or no symptoms categories.
Inclusion Criteria:

 -  CIC/PBS- patients with urinary tract pain or discomfort and dysuria that is present
 for > 6 months and is not due to acute urinary tract infection, stones or other
 urinary pathology.

 -  rUTI- patients with greater that 2 urinary tract infections in 6 months or greater
 than 3 urinary tract infections in one year. A UTI is defined as - symptomatic
 complaints of dysuria, increased frequency of urination, and hesitancy to urinate and
 a clean catch urinary culture with >103 colony counts of bacteria per milliliter.

 Exclusion Criteria:

 -  Inability to provide written informed consent

 -  Inability or unwillingness to adhere to 40 HBOT treatment sessions over an 8-10 week
 time period or to complete follow up questionnaires/telephone contacts.

 -  Confinement anxiety and inability to enter the hyperbaric chamber for a 90 minutes
 treatment session.

 -  Inability to effectively equalize the middle ear during changes in ambient pressure.
 This will include patients with a history of tympanic membrane perforation, head and
 neck surgery with compromised Eustachian tube function, including but not limited to
 tracheostomy, mastoidectomy, middle ear surgical procedures and cochlear implants.

 -  Presence of an indwelling urinary catheter

 -  Any acute or chronic urinary condition that is not rUTI or CIC/PBS- such as but not
 limited to urinary bladder stones, tumors, urinary retention, adynamic urinary
 bladder, chemotherapy related hemorrhagic cystitis, radiation cystitis or other
 pathology.

 -  Active or uncontrolled cancer diagnosis.

 -  Active or uncontrolled psychiatric disease.

 -  American Heart Association Class III or greater congestive heart failure or
 symptomatic coronary artery disease.

 -  Active or uncontrolled pulmonary diseases- including asthma, COPD, bullous lung
 disease, previous thoracotomy, pneumothorax or history of pneumothorax.

 -  Acute upper respiratory tract infection.

 -  End stage renal disease receiving hemo- or peritoneal dialysis

 -  Active or history of seizure disorder

 -  Hemolytic blood dyscrasias

 -  History of exposure to bleomycin

 -  Presence of a pacemaker or epidural pain pump

 -  Pregnant or lactating women

 -  Patients with type 2 diabetes

 -  Patients with neurovascular diseases (e.g. recent stroke)

 -  Patients with uncontrolled hypertension

 -  Patients with retinitis pigmentosa

 -  Patients taking the following concomitant medications: PDE5 inhibitors, carbonic
 anhydrase inhibitors, beta blockers, alpha blockers, nitrates.