The study will evaluate the injection of AMDC for Urinary Sphincter Repair (USR) compared to a placebo dose, with the hypothesis that one or two treatments of AMDC is statistically superior to placebo at 12 months following the initial treatment.
ID
Source
Brief title
Condition
- Urinary tract signs and symptoms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The principle objective of the study is to determine the effectiveness and
safety of Autologous Muscle-Derived Cells (AMDC) in the treatment of female
patients with stress urinary incontinence.
Effectiveness: Is treatment with AMDC effective at 12 months after treatment
in reducing the number of stress incontinence episodes or reducing the pad
weight?
Safety: Are the side effects or medical events associated with AMDC treatment
compared to the benefit acceptable after 12 months?
Secondary outcome
For secondary objectives, the study will examine if effectiveness is maintained
long term (2 years). The study will also look at how the AMDC treatment
affects the quality of life of the patients, which will use a number of quality
of life assessments. Safety will also be examined at timepoints other than 12
months.
Background summary
Stress Urinary Incontinence (SUI) is a common condition that primarily affects
women. SUI is the involuntary leakage of urine on effort or exertion, or on
sneezing or coughing. SUI symptoms can occur for two reasons: 1) loss of
support in the pelvic floor or bladder or 2) sphincter muscle (muscle around
the urethra) function deficiency.
Current treatments for SUI include surgery for slings or injections of bulking
agents. Both of these treatments have some disadvantages. Surgery for slings
usually involves general anesthesia, catheters that need to be removed later,
and a hospital stay. All of these can be a burden for the patient or cause
delays in recovery. Disadvantages of collagen injections include loss of
effectiveness, the need for repeat injections, high cost, and allergic
responses to collagen. Other substances used for bulking injections include
synthetic materials or autologous fat (a patient*s own fat). Although these
substances have provided evidence for safety of the injection technique, the
success of these materials is hindered by the need for multiple injections, and
by migration of material. These disadvantages limit the overall success of
injection therapy. Ideally, the most successful agent would be durable,
non-immunogenic (does not provoke immune response in recipient) and
non-migratory (stays in place).
Cook MyoSite Incorporated Autologous Muscle Derived Cells (AMDC) consists of
muscle progenitor cells isolated from skeletal muscle tissue that are
subsequently propagated ex vivo. Following propagation it is verified that the
cells exhibit attributes of functional muscle cells (demonstrated through a
potency assay). Once functionality is verified, the cells are delivered into a
tissue structure that is likely to benefit from additional muscle function
(e.g. the urethra sphincter).
The proposed study will determine the effectiveness and safety of Cook MyoSite
Incorporated Autologous Muscle-Derived Cells (AMDC) in the treatment of SUI in
female patients. The study will evalutate the injection of AMDC compared to a
placebo dose. It is believed that the cells (AMDC) become part of the tissue
where they have been injected. In theory, this may help patients to have more
control over urine storage and release (peeing). It may also decrease urinary
leakage problems, although this is not guaranteed.
The proposed treatment has some advantages when compared to surgery or bulking
agents. Injections with AMDC are designed to be an outpatient procedure that
does not require general anesthesia, catheters that need to be removed, or a
hospitality stay. The procedures involved are all designed to be completed in a
clinic with local anesthetics. If a catheter is used for any part of the
procedure, it does not remain in place, and the patient does not need to have
it removed at a later date.
Study objective
The study will evaluate the injection of AMDC for Urinary Sphincter Repair
(USR) compared to a placebo dose, with the hypothesis that one or two
treatments of AMDC is statistically superior to placebo at 12 months following
the initial treatment.
Study design
The study design under consideration is a randomized, double-blind,
placebo-controlled, multicenter study to determine the effectiveness and safety
of AMDC in the treatment of stress urinary incontinence in female patients.
The study will randomize patients to receive one of two doses (placebo or 150 x
10^6 cells) and either one or two treatments. The allocation ratio will be 2:1
(cells: placebo), while one and two treatments are equally allocated (1:1). A
patient*s randomization assignment will occur at enrollment. The study will
treat a total of 246 patients (164 treated with 150×10^6 AMDC and 82 treated
with placebo). Those patients randomized to the two treatment groups will
receive the same dosage at the 6 month visit that they received at the initial
treatment. Placebo injected patients will be given the opportunity to receive
the 150 x 10^6 cell dose following the 12 month evaluation.
Intervention
All eligible patients consenting to study participation will have skeletal
muscle tissue harvested using a needle biopsy during an initial outpatient
procedure. The harvested muscle tissue will be placed in a hypothermic medium
and transported to the manufacturer for processing in their cell processing
facility in Pittsburgh, PA, USA. The muscle derived cells (MDC) will be
isolated and propagated in culture over several weeks to the final dose of 150
x 10^6 for the cell treated groups.
After reaching the desired concentration, the isolated and expanded AMDC will
be frozen and shipped back to the investigating physician. The physician will
thaw the product (either the cell dose or the acellular cryogenic medium
placebo control as assigned per the randomization) and dilute the sample with
an equal volume of physiological saline. The resulting suspension will be
injected into the patient*s urethral sphincter in a brief outpatient
procedure.
Study burden and risks
Risks of participation in the study include those associated with:
Cellular injection: Rare potential risks include an allergic or immune response
to AMDC (cells or components of the final formulation including: bovine
proteins, ampicillin, and gentamicin sulfate), and infection. Risk of allergic
or immune response to the cells is expected to be minimal due to the use of
autologous cells. Risk of allergic response to bovine proteins, ampicillin, and
gentamicin sulfate used in AMDC production should be minimal since only trace
amounts are expected to be in the final product. The risk of infection is
expected to be consistent with similar procedures (e.g. cystoscopy).
Additional risks include transient dysuria, urgency, or altered micturition
frequency.
Since the side effects of muscle cell injection in the urinary passage on
reproduction have not been determined, highly effective methods of
contraception should be used for the duration of a patient*s involvement in the
trial and for two weeks after the last study visit. The investigator should
discuss with their patients appropriate birth control methods (double barrier
method) which need to be followed for the period of one month prior to the
injection visit and continuing until at least two weeks following the last
study visit. If the patient has a positive pregnancy test at the biopsy visit,
the study staff is not to biopsy the patient, and the patient is then excluded
from the study. Additionally, if the patient has a positive pregnancy test on
the day of injection the study staff is likewise instructed not to inject the
patient, and the patient is excluded from the study.
Cystoscopy:The risks of cystoscopy are expected to be infrequent, and include
the possibility of discomfort, mild cramps, bleeding, excessive trauma, and
infection. Side effects that are rare include inability to urinate after the
procedure and puncture of the bladder or urethra.
Muscle biopsy: Infrequent potential risks include the possibility of wound
infection, hematoma, bleeding, and local pain. Rare potential risks include
scarring.
Urinary catheterization: The risks of urinary catheterization are expected to
be infrequent and include the possibility of transient inability to void,
bleeding (hematuria), discomfort or pain during catheter insertion, cramps, and
urinary tract infections.
Venipuncture: The risks from venipuncture include bleeding, discomfort,
light-headedness, pain, bruising, and rarely, an infection at the site where
blood is drawn.
Additional risks are expected to be comparable to those associated with
standard treatment using collagen injections. These include the possibility of
urinary retention and infection. In addition, mild reactions such as swelling
and local irritation may be associated with topical anesthetics used during the
injection procedure.
Because this study includes experimental procedures, not all risks and outcomes
can be foreseen.
This study will provide information on the safety and effectiveness of the
cellular injection in the therapy of urinary incontinence and may help
determine how to improve treatment of urinary incontinence. Other patients in
the future may benefit from the knowledge gained from this study.
Sandet 6
Bjaeverskov 4632
DK
Sandet 6
Bjaeverskov 4632
DK
Listed location countries
Age
Inclusion criteria
• The patient is female and has primary symptoms af SUl, as confirmed by patient medicai h istory and clinical symptoms, including a focused incontinence evaluation.
Exclusion criteria
• Patient has symptoms af pure urge incontinence as confirmed by basic evaluation af etiology from a patient medical history, including a focused incontinence history.
• Patient has symptoms af mixed urinary incontinence where urge incontinence is the predominant factor.
• Patient has had stress urinary incontinence symptoms less than 6 months prior to signing the informed consent.
• Patient has not previously attempted conservative treatment for at least 1 month prior to signing the informed consent. (Examples of conservative treatment include behavior modifications, bladder exercises, biofeedback, etc.)
• Patient has more than 2 episode af awakening to void during normal sleeping hours.
• Patient cannot be ma intained on a stable dose and/or frequency of medication (including diuretics) known to affect lower urinary tract function, including but not limited to, anticholinergics, tricyclic antidepressants or alpha-adrenergic blockers, for at least 2 weeks prior to randomization or is likely to change during the course af the study.
• Patient is pregnant, lactating, or plans to become pregnant during the course of the study.
• Patient refuses to provide written informed consent.
• Patient is not at least 18 years of age.
• Patient is not available for the follow-up evaluations as required by the protocol.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-003599-35-NL |
| ClinicalTrials.gov | NCT01382602 |
| CCMO | NL41963.000.13 |