Urinary Tract Infections, Spinal Cord Injuries, Spinal Cord Diseases, Neurogenic Bladder
Conditions
Brief summary
A non-randomized study evaluating the efficacy of intravesical gentamicin on the occurrence rate of urinary tract infections and bladder complications in patients after spinal cord injury (SCI), and to assess its effectiveness in promoting overall quality of life (QOL), community living, and participation.
Detailed description
Intervention: Participants' number of UTIs during the six-month treatment period will be compared to the number they incurred during the six months prior to treatment. Participants complete a baseline visit which consists of medical history, informed consent, urinalysis/culture indicating no active UTIs, metabolic panel, and self-reported measures about complications, symptoms, community participation and quality of life. Similar information is collected at the end of treatment. At a 3-month follow up visit, all available data is obtained through phone interviews and/or medical chart reviews except for self-report measures. Participants begin active treatment using Gentamicin plus saline solution after they have completed all requirements. Instillations of treatment solution occur nightly after the participant's last evening catheterization. Bi-weekly calls are conducted to ensure compliance, answer questions and document adverse events. Participants will stop the trial if they develop an UTI. After receiving treatment for the UTI by their physician, they will go into a washout period of a week before resuming the trial with Gentamicin instillations.
Interventions
Gentamicin is compounded by the Michigan Medicine Research Pharmacy in a concentration of 480 milligrams of the active product to 1000 milliliters of normal saline. Pharmacy mails participants treatment drug. Once received, participants will do daily instillations of 30 milliliters of solution after catheterizing their bladder at night.
Sponsors
Department of Health and Human Services
University of Michigan
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
For each participant, six month pre-treatment data is compared to data collected during treatment (count of UTIs) and immediately after treatment (self-reported measures).
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Provision of signed and dated informed consent form and agreement to complete the daily dosing log as instructed by the study coordinator. * History of traumatic spinal cord injury (SCI) or non-traumatic spinal cord disease, (SCD) with sustained neurological dysfunction * At least 6 months post-initial hospital discharge following SCI/SCD onset * Neurogenic bladder * Ability to perform daily instillation on self or with help of others and willingness to adhere to the study regiment. * History of at least 2 documented urinary tract infection (UTI) during the previous 6 months (prior to screening) * Have a designated physician or health care provider for routine care * Use of clean intermittent catheterization or catheterization through a stoma (i.e. Mitrofanoff) as their primary method of bladder management
Exclusion criteria
* Concurrent use of systemic oral or intravesical antibiotic prophylaxis * Documented or self-reported history of gentamicin allergy * Female patients who are currently pregnant or attempting to become pregnant * Patients with a history of 8th cranial nerve disorder * Co-morbidities like cancer and chronic disease that could impact patient safety OR significantly affect the rate of UTIs and/or quality of life (QOL) substantially * Urological co-morbidities like bladder cancer and history of kidney disease. * Current UTI at screening (assessed via urine analysis and culture and symptoms) * Concurrent enrollment in a similar clinical trial * Concurrent use of contraindicated diuretics (ethacrynic acid, furosemide) * Current use of other contraindicated or disallowed concomitant medications or receiving treatments that may influence the results from this study. * Known allergy to aminoglycoside antibiotics; Otological symptoms at baseline (i.e. tinnitus. severe dizziness/vertigo) * At the discretion of study team, individuals who are unable or unlikely to comply with procedures and/or for whom study participation is not recommended (e.g. unable to arrange transportation, cognitive and/or behavioral challenges that preclude meaningful participation, poor health, etc.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Urinary Tract Infections (UTI) Over Time | 6 months prior to treatment and 6 months during treatment | Number of reported urinary tract infections (UTI) by participants and documented in medical chart, per person across months pre and post treatment. The number of UTIs over time was determined by establishing a per person-month rate made up of the total number of UTIs pre and during treatment (numerator) for the sample divided by the total number of persons/ 6 months (11 participants over 6 months period = 66) as the denominator. The unit of measure is defined as pre and during treatment number of UTI events per person months. These appear below under outcome measure data table. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Score of Neurogenic Bladder Symptom Severity (NBSS) Scale | Baseline to 6 months | Self-reported bladder symptoms on a scale from 0 (no symptoms) to 74 (maximum symptoms). The NBSS is a patient reported 22 item scale designed to assess symptoms and bladder related consequences among persons with neurogenic bladder dysfunction. NBSS scores are calculated across three domains with higher scores being worse and reflecting more symptoms or complications. Incontinence (scored 0-29), storage and voiding (scored 0-22), and consequences (scored 0-23). An additional question of happiness (points) was not used for this outcome. |
| Change in Score of Neurogenic Bowel Dysfunction (NBD) | Baseline to 6 months | Self-reported bowel symptoms on a scale from 0 (very minor) to 14+ (severe). The NBD is a 10 item validated measure that assesses frequency of defecation and methods of bowel management and complications. Thus negative numbers in score change represent decrease in symptom severity. |
Countries
United States
Participant flow
Pre-assignment details
Of 23 eligible persons who consented, only 19 started on treatment due to several reasons including changes in necessary study procedures associated with the COVID outbreak, changes in medical status due to complications and personal decisions to proceed with treatment.
Participants by arm
| Arm | Count |
|---|---|
| Gentamicin Sulfate Participants initiate Gentamicin instillations every night for a period of 6 months. Instillations are stopped if they developed a UTI. After receiving treatment they can continue with the Gentamicin instillations. After baseline and consented they are instructed on how to do the instillations through a catheter, once they receive the drug and aid equipment (i.e. syringes) to do installations. Remaining drug is to be disposed after each use. Participants use their own catheters. In-dwelling catheters are not allowed.
Gentamicin Sulfate: Gentamicin will be compounded by the Michigan Medicine Research Pharmacy in a concentration of 480 milligrams of the active product to 1000 milliliters of normal saline. Participants will do daily instillations of 30 milliliters of solution | 19 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | First cohort faced a clinical hold which caused disruption in treatment; | 4 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Physician Decision | 3 |
| Overall Study | Second cohort faced changes due to pandemic, resulting in declining participant count | 2 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Gentamicin Sulfate |
|---|---|
| Age, Continuous | 46 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 18 Participants |
| Region of Enrollment United States | 19 Participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 12 Participants |
| Type of spinal lesions Spinal Cord Disease (SCD) | 5 Participants |
| Type of spinal lesions Spinal Cord Injury (SCI) | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 19 |
| other Total, other adverse events | 17 / 19 |
| serious Total, serious adverse events | 4 / 19 |
Outcome results
Primary
Number of Urinary Tract Infections (UTI) Over Time
Number of reported urinary tract infections (UTI) by participants and documented in medical chart, per person across months pre and post treatment. The number of UTIs over time was determined by establishing a per person-month rate made up of the total number of UTIs pre and during treatment (numerator) for the sample divided by the total number of persons/ 6 months (11 participants over 6 months period = 66) as the denominator. The unit of measure is defined as pre and during treatment number of UTI events per person months. These appear below under outcome measure data table.
Time frame: 6 months prior to treatment and 6 months during treatment
Population: Eleven participants with spinal cord injury or disease and neurogenic bladder with recurrent urinary track infections (2 or more) during the 6 months prior to treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Gentamicin Sulfate | Number of Urinary Tract Infections (UTI) Over Time | 6 months prior to treatment | 0.53 UTI events per person months. |
| Gentamicin Sulfate | Number of Urinary Tract Infections (UTI) Over Time | 6 months during treatment | 0.09 UTI events per person months. |
Comparison: comparison between pre and during treatment rates of UTIp-value: <0.000195% CI: [0.03, 0.2]differences in incidence rate ratio
Secondary
Change in Score of Neurogenic Bladder Symptom Severity (NBSS) Scale
Self-reported bladder symptoms on a scale from 0 (no symptoms) to 74 (maximum symptoms). The NBSS is a patient reported 22 item scale designed to assess symptoms and bladder related consequences among persons with neurogenic bladder dysfunction. NBSS scores are calculated across three domains with higher scores being worse and reflecting more symptoms or complications. Incontinence (scored 0-29), storage and voiding (scored 0-22), and consequences (scored 0-23). An additional question of happiness (points) was not used for this outcome.
Time frame: Baseline to 6 months
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Gentamicin Sulfate | Change in Score of Neurogenic Bladder Symptom Severity (NBSS) Scale | NBSS Incontinence (0-29) | -3.8 score on a scale |
| Gentamicin Sulfate | Change in Score of Neurogenic Bladder Symptom Severity (NBSS) Scale | NBSS Storage/Void (0-22) | -1.1 score on a scale |
| Gentamicin Sulfate | Change in Score of Neurogenic Bladder Symptom Severity (NBSS) Scale | NBSS Consequences (0-23) | -1.9 score on a scale |
Comparison: NBSS Domain score for incontinence pre-post comparison; small sample size did not allow for power calculation.p-value: <0.0695% CI: [-7.9, 0.3]t-test, 2 sided
Comparison: NBSS Domain score for storage and voiding; pre-post comparison. Due to small sample size (n=11) no power calculations were conducted.p-value: <0.3995% CI: [-3.8, 1.7]t-test, 2 sided
Comparison: Pre and post test comparisons of mean NBSS scores for the consequences domain. Power calculations were not conducted due to small sample size.p-value: <0.1495% CI: [-4.6, 0.8]t-test, 2 sided
Secondary
Change in Score of Neurogenic Bowel Dysfunction (NBD)
Self-reported bowel symptoms on a scale from 0 (very minor) to 14+ (severe). The NBD is a 10 item validated measure that assesses frequency of defecation and methods of bowel management and complications. Thus negative numbers in score change represent decrease in symptom severity.
Time frame: Baseline to 6 months
Population: 11 participants with spinal cord injury or disease (SCI/D) with neurogenic bladder and recurrent UTIs during 6 months prior to treatment. They completed the NBD survey.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Gentamicin Sulfate | Change in Score of Neurogenic Bowel Dysfunction (NBD) | -2.1 score on a scale |
p-value: <0.3495% CI: [-6.8, 2.6]t-test, 2 sided