Tissue Bonding Cystostomy(TBC)
Tissue Bonding Cystostomy(TBC)
Spinal Cord Injured [SCI] patients typically cannot "pee". Injury to the spinal cord disrupts
 the in-coming and out-going brain signals that coordinate bladder sensation and the emptying
 of bladder. SCI typically causes chronic retention of urine with uncontrolled leakage of
 urine. Some form of tube (catheter) is needed to drain the urine except with the mildest
 forms of SCI. Two types of tubes to drain the urine have been used for many years. These
 types are the urethral (inserted into the bladder through the opening usually used to empty
 the bladder) and abdominal, called suprapubic cystostomy tubes (put into the bladder through
 the abdomen).

 Bacteria (germs) normally live on our skin. Bacteria have sticky surfaces and so they stick
 to catheter surfaces. Bacteria reproduce very rapidly from a few dozen to over a million in
 24 hours. In a warm liquid environment, like urine, bacteria can reach a density of 10
 million per cubic centimeter in 48 hours which causes infection. Oral drugs and
 antibiotic-coated catheters delay this process by a week or two, but within a month 100% of
 patients have bacteria in their urine. Existing drugs cannot eliminate these microbial
 sanctuaries.

 The TBC is a 'closed access' abdominal drainage tube that has a 'cuff' or 'anchor'. It is
 permanently placed in the abdominal muscle to bond with the body's tissue. Another catheter
 is temporarily connected to the TBC that is easily replaceable in the clinic without
 anesthesia or special instruments. It locks to form a water-tight system. Many parts of the
 TBC are coated with an antibacterial substance that will delay the growth of bacteria. The
 TBC has been used with success in multiple animal studies.

 This is a Phase I human clinical trial in which the TBC will be used 10 spinal cord injured
 patients, each of whom will be followed for 12 months or longer. Abdominal catheter exit
 sites will be photographed monthly and tested periodically to document growth of any
 bacteria. Every three months, patients will complete satisfaction questionnaires and their
 urine will be tested for bacteria. Urine will also be tested as clinically indicated.
Traumatic spinal cord injury (SCI) results in permanent paraplegia or quadriplegia in
 approximately 10,000 Americans annually. All patients with SCI have neuropathic dysfunction
 of the urinary bladder. Progressive neurological syndromes such as multiple sclerosis,
 Parkinson's disease, Stroke, hemiplegia and dementia also induce progressive neuropathic
 bladder dysfunction. Neurologic impairment of the bladder causes or contributes to chronic
 urinary retention or urinary incontinence or both. Several million Americans suffer chronic
 neuropathic urinary retention or incontinence or both. Males tend to develop urinary
 retention and females tend to develop urinary incontinence but both genders commonly develop
 elements of both.

 Current management includes [a] indwelling tubes (urethral catheterization or [b] suprapubic
 (abdominal) catheterization, [c] intermittent urethral catheterization [4+times per day], and
 surgical rehabilitation [e.g. use of autogenous intestinal conduits or reservoirs]. No single
 form of management is ideal. A high percentage of elder and disabled patients are poor
 candidates or non-candidates for surgical rehabilitation because of co-morbidities or limited
 life expectancy. A majority of neurologically impaired patients are managed with chronic tube
 drainage of their bladders [e.g. a-c, above].

 Traditional tube drainage of the bladder may be either via the urethra or via an intubated
 fistula in the lower abdomen. Intermittent catheterization-by the patient or a care
 giver--via the urethra is a well accepted and sometimes used method. This technique is
 occasionally used [by an attendant] in cognitively impaired patients or quadriplegics with
 impairment of the upper extremities. Intermittent catheterization is expensive when provided
 by a professional care giver and is a social and domestic burden when provided by a family
 member. In most chronically impaired [cognitively or physically] patients chronic indwelling
 urethral or suprapubic tubes evolve as the most practical and widely used treatment option.

 Chronic urinary infection and bladder stones are recurrent problems in patients who use
 indwelling tubes. Foley urethral catheters [which are also commonly used as suprapubic tubes]
 are licensed for 30 day use by FDA.

 Indwelling urethral catheters and suprapubic tubes are "open eco-systems' and provide easy
 access to skin flora. Skin microbes migrate along the tubes and gain access to bladder urine
 which becomes colonized in 100% of cases. Both gram-stain positive [gram +] and gram-stain
 negative [gram-] organisms easily gain access to bladder urine. Both type of microbes form
 biofilms on the catheters within 48 hours of colonization. The biofilms are microbial
 sanctuaries that are highly resistant to eradication with antibiotics. Use of antimicrobial
 agents [often for non-urinary indications] may eradicate common urinary pathogens and thereby
 'select' more resistant organisms. Multiple organisms and resistant organisms are commonly
 grown from the bladders of neurologically impaired patients who utilize indwelling urethral
 or suprapubic tubes. Both types of tubes tend to induce bladder spasms and urinary leakage
 thereby soiling under-garments and bed clothes. A majority of such patients smell of
 urine-chronically.

 Urine is normally supersaturated with dissolved salts, notably physiologic concentrations of
 calcium, phosphorus, oxalic acid, and magnesium. Foreign bodies [e.g. the indwelling tube']
 initiate nucleation of the salts which then precipitate and form stones on the catheters. A
 high percentage of neurologically impaired patients have Proteus species of chronic
 bacteriuria. These urea-splitting [urease producing] organisms greatly accelerate formation
 of struvite [magnesium-ammonium-phosphate] stones on the catheters; rapid stone formation may
 necessitate catheter exchanges more frequently than monthly.

 Significant expense attends the chronic use of traditional urinary catheters. Monthly travel
 to clinics and monthly replacement of the drainage catheter and management of febrile
 reactions which may be precipitated by tube changes are routine and expensive. Surgical
 procedures are commonly required to remove bladder, kidney or ureteral stones that develop as
 a consequence of the chronic bacteriuria. Soiled garments and beds and the prevailing order
 of urine cause many disabled patients to be put in to assisted care facilities.
Inclusion Criteria:

 -  Age 18 and older that have spinal cord injury and/or chronic, irreversible neuropathic
 bladder dysfunction from other progressive neurological syndromes including Stroke,
 multiple sclerosis and Parkinsonism.

 -  Candidates must have a minimum duration of injury and bladder dysfunction of 2 years

 -  Candidates shall be those who utilize:

 -  an indwelling Foley catheter,

 -  an indwelling suprapubic catheter,

 -  diapers or

 -  external (condom) catheter drainage or intermittent self-catheterization but
 finds the current alternative to be socially unsatisfactory.

 -  Candidates need to recognize the investigational nature of the "tissue bonding
 cystostomy" device and must be willing to return for periodic follow-up.

 -  Candidates also need to recognize that a minor surgical procedure may be needed to
 remove the device if it proves unsatisfactory.

 -  Patients must be willing and capable of signing the Informed Consent Document (ICD).

 -  In the feasibility study detailed in this protocol only English-speaking subjects will
 be accepted for participation. If the protocol is expanded then a Spanish-language
 consent form will be developed and Spanish-speaking candidates will be accepted.

 Exclusion Criteria:

 -  have a reversible spinal cord injury or a reversible neurological illness

 -  have been injured less than two years

 -  have acceptable forms of urological management utilizing intermittent
 self-catheterization, or

 -  spontaneous voiding with the use of an external collecting appliance.

 -  have no advanced neuropathic bladder dysfunction of less than 2 years duration

 -  have advanced neuropathic bladder dysfunction and are happy with intermittent
 self-catheterization or more traditional forms of tube drainage are non-candidates.

 -  This feasibility study will exclude females of child-bearing age. In subsequent
 expanded clinical trials it may be appropriate [depending on the outcome of the
 feasibility study] to include females of child-bearing age.