Hyperbaric Oxygen Therapy for Inflammatory Conditions of the Urinary Bladder

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.