Benign Prostatic HyperplasiaPhase 2MIST2NCT00451191

Botulinum Toxin Injection for the Management of BPH

A Phase 2 study testing botulinum toxin type A (BoNT/A) in people with Benign Prostatic Hyperplasia, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 7 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This is a double-blind randomized phase II trial to determine whether two different doses of BoNT/A injection into the prostate gland demonstrate sufficient improvement in the management of lower urinary symptoms due to BPH to warrant more extensive research. Subjects will receive either a 100U or 300U dose. Read more about this study

Who is it for?: Ages 50 years and older, men only
Conditions the study is for: Benign Prostatic Hyperplasia
What is being tested?: botulinum toxin type A (BoNT/A)
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 134 participants
Where: 7 sitesUnited States
Study dates: Oct 2006to Dec 2009
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 50 years and older
Men only
No healthy volunteers
Adult, Older adult

Who may be able to join

Male at least 50 years of age.
Voided volume => 125 ml.
Maximum urinary flow < 15 ml/sec.
AUA symptom severity score => 8.
Patient signed informed consent prior to the performance of any study procedures.
Patient able to complete the study protocol in the opinion of the investigator.

Who cannot join

Any prior surgical intervention for BPH.
Current diagnosis of acute or chronic prostatitis (which may cause LUTS that mimic BPH).
Overactive bladder without bladder outlet obstruction.
Enrolled in another treatment trial for any disease within the past 30 days.
Men interested in future fertility.
Previous exposure to botulinum toxin.

Show all 27Show fewer

On alpha-blocker within the past 48 hours.
On any 5-alpha-reductase inhibitor within the past month.
Post void residual > 350 ml.
On phenylephrine, pseudoephedrine, imipramine, an anticholinergic, or cholinergic medication within the past 2 weeks.
On estrogen, androgen, any drug producing androgen suppression, or anabolic steroids within the past 4 months.
Clinically significant renal or hepatic impairment as determined by abnormal creatinine or AST levels (based on local institutional values).
Serum prostate specific antigen level > 8 ng/ml (Hybritech). For those with a PSA between 4-8 ng/ml, the PSA elevation must be considered to be from a benign cause in the opinion of the PI. This decision can be based on PSA velocity, previous TRUS biopsy, percent free PSA, or other clinical estimations in keeping with sound urologic care.
Active urinary tract disease or biopsy of the prostate within the past 6 weeks.
Daily use of a pad or device for incontinence required.
Episode of unstable angina pectoris, myocardial infarction, transient ischemic attack, or cerebrovascular accident (stroke) within the past 6 months.
On aminoglycosides or any drug that interfere with neuromuscular transmission.
Eaton-Lambert syndrome, hemophilia, hereditary clotting factors deficiency, or bleeding diathesis.
Penile prosthesis or artificial urinary sphincter.
History or current evidence of carcinoma of the prostate or bladder, pelvic radiation or surgery, urethral stricture, or bladder neck obstruction.
Known primary neurologic conditions such as multiple sclerosis, myasthenia gravis or Parkinson's disease, or other neurological diseases known to affect bladder function.
Documented bacterial or acute prostatitis within the past year.
Two documented urinary tract infections of any type in the past year (UTI defined as > 100,000 colonies per ml urine from midstream clean catch or catheterized specimen).
History of bladder calculi.
Patients must be off aspirin, NSAIDS, and Coumadin for 7 or more days prior to botulinum toxin injection.
Cancer that is not considered cured, except basal cell or squamous cell carcinoma of the skin (cured defined as no evidence of cancer within the past 5 years).
Any serious medical condition likely to impede successful completion of the study, such as certain mental disorders, hypersensitivity to botulinum toxin or anesthetics used in the study, syncope, uncontrolled diabetes.

Trial locations and contacts

7 sites in 1 country.

City, postcode or hospital

7 sites in 1 country

United States7 sites

Northwestern University
Chicago, Illinois, 60611
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
University of Colorado Health Sciences Center
Denver, Colorado, 80010
Baylor College of Medicine
Houston, Texas, 77030
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Cornell University
New York, New York, 10021
Mayo Clinic
Rochester, Minnesota, 55905

Other trials in United States

About this study

Official title: Intraprostatic Injection of Botulinum Toxin for the Management of Benign Prostatic Hyperplasia: A Randomized Phase II Trial

Conditions: Benign Prostatic Hyperplasia
Being tested: botulinum toxin type A (BoNT/A)
Keywords: benign prostatic hyperplasia, BPH, botulinum toxin, BoNT/A
Medical subject headings: Prostatic Hyperplasia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

botulinum toxin type A (BoNT/A)Drug
Also called marketed in the US as BOTOX by Allergan
100 unit and 300 unit dosages: Dilute each 100 U vial with 1.3 ml of normal saline. Each reconstituted vial is then drawn up into a single syringe with a total of 4 ml = 300 U. The instrument used to inject the botulinum toxin is an ultrasound device with a transrectal ultrasound probe specially designed for prostate biopsies which has a special canal to introduce and direct a needle in to the selected prostatic area.

Study groups in NCT00451191
Study group	Role	What they receive
1	Active comparator	100 units botulinum toxin type A (BoNT/A) Receives: Drug: botulinum toxin type A (BoNT/A)
2	Active comparator	300 units botulinum toxin type A (BoNT/A) Receives: Drug: botulinum toxin type A (BoNT/A)

What is being measured

The primary outcome is the main question the study is designed to answer.

Improvement in the AUA Symptom Score Index by 30% From Baseline Within the First 12 Weeks After Injection.
The primary outcome was treatment success at 3 months post-treatment, defined as (1) improvement in the AUASI by at least 30% and/or (2) Qmax improvement of more than 30%, each determined from baseline to 3 months after injection. In addition, two safety criteria also had to be met; a dose failed if (1) any reported event was determined to be related to the onabotulinum toxin A injection and was considered life threatening, disabling, or fatal or (2) >=40% of the participants reported a moderate or severe side effect related to the botulinum toxin injection.
Measured: 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 2006Dec 2009

First posted23 Mar 2007 (estimated)
Study startOct 2006
Primary completionJun 2009
Study completionDec 2009

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Benign Prostatic HyperplasiaStudies of the same condition, open and under way.
More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 134 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00451191
Sponsor's protocol ID: MIST2
Other IDs: U01DK060817
Acronym: MIST2
Status last verified: Apr 2020
First submitted: 21 Mar 2007
Last updated: 21 Apr 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: Data are available at the NIDDK Central Repository https://repository.niddk.nih.gov/studies/mist2/?query=mist

Publications

Crawford ED, Hirst K, Kusek JW, Donnell RF, Kaplan SA, McVary KT, Mynderse LA, Roehrborn CG, Smith CP, Bruskewitz R. Effects of 100 and 300 units of onabotulinum toxin A on lower urinary tract symptoms of benign prostatic hyperplasia: a phase II randomized clinical trial. J Urol. 2011 Sep;186(3):965-70. doi: 10.1016/j.juro.2011.04.062. Epub 2011 Jul 24.
PubMed 21791356

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Clinical Study on Prostate Thermal Vapor Ablation Guided by MRI/TRUS Fusion Imaging
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Active, not recruitingPhase 4
Standard Versus Double Alpha Blockers Treatment for Symptomatic Benign Prostatic Obstruction
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Learning Curve of Tri-lobar HoLEP Versus En-bloc HoLEP
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All Benign Prostatic Hyperplasia trials

Study at a glance

From the registry record, last updated by the sponsor on 21 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Intraprostatic Injection of Botulinum Toxin for the Management of Benign Prostatic Hyperplasia: A Randomized Phase II Trial
ClinicalTrials.gov ID: NCT00451191
Acronym / sponsor ID: MIST2 / MIST2
Conditions: Benign Prostatic Hyperplasia
Keywords: benign prostatic hyperplasia, BPH, botulinum toxin, BoNT/A
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 134 participants (actual)
Lead sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
Collaborators: George Washington University
Study start: Oct 2006 (actual)
Primary completion: Jun 2009 (actual)
Study completion: Dec 2009 (actual)
First posted: 23 Mar 2007 (estimated)
Results: Posted 24 Jun 2013

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
1	Active comparator	Drug: botulinum toxin type A (BoNT/A)100 units botulinum toxin type A (BoNT/A)
2	Active comparator	Drug: botulinum toxin type A (BoNT/A)300 units botulinum toxin type A (BoNT/A)

Who may qualify

Ages: 50 years and older
Sex: Male only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

Male at least 50 years of age.
Voided volume => 125 ml.
Maximum urinary flow < 15 ml/sec.
AUA symptom severity score => 8.
Patient signed informed consent prior to the performance of any study procedures.

Key exclusion criteria (27 listed)

Any prior surgical intervention for BPH.
Current diagnosis of acute or chronic prostatitis (which may cause LUTS that mimic BPH).
Overactive bladder without bladder outlet obstruction.
Enrolled in another treatment trial for any disease within the past 30 days.
Men interested in future fertility.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
botulinum toxin type A (BoNT/A)Also: marketed in the US as BOTOX by Allergan100 unit and 300 unit dosages: Dilute each 100 U vial with 1.3 ml of normal saline. Each reconstituted vial is then drawn up into a single syringe with a total of 4 ml = 300 U. The instrument used to inject the botulinum toxin is an ultrasound device with a transrectal ultrasound probe specially designed for prostate biopsies which has a special canal to introduce and direct a needle in to the selected prostatic area.	Drug	1, 2

Primary outcome

Improvement in the AUA Symptom Score Index by 30% From Baseline Within the First 12 Weeks After Injection.
Time frame: 12 weeks
The primary outcome was treatment success at 3 months post-treatment, defined as (1) improvement in the AUASI by at least 30% and/or (2) Qmax improvement of more than 30%, each determined from baseline to 3 months after injection. In addition, two safety criteria also had to be met; a dose failed if (1) any reported event was determined to be related to the onabotulinum toxin A injection and was considered life threatening, disabling, or fatal or (2) >=40% of the participants reported a moderate or severe side effect related to the botulinum toxin injection.

Results and safety

Results posted to the registry on 24 Jun 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
100 Units Botulinum Toxin Type A	68	53
300 Units Botulinum Toxin Type A	66	55

Primary outcome: Improvement in the AUA Symptom Score Index by 30% From Baseline Within the First 12 Weeks After Injection.

Time frame: 12 weeks. Number. Unit: participants

Measure	100 Units Botulinum Toxin Type A n = 53	300 Units Botulinum Toxin Type A n = 55
Value	46	50

100 Units Botulinum Toxin Type A vs 300 Units Botulinum Toxin Type A: p <0.05, Simon's optimal two-stage design

Population analysed: By the last 12-month follow-up visit, 15 men (22%) in the 100 U dose arm and 11 (17%) in the 300 U dose arm had withdrawn due to dissatisfaction with treatment results or continued to attend study follow-up but received additional alternate treatment prior to 12 months.

Adverse events

Time frame: 12 months. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
100 Units Botulinum Toxin Type A	7 of 68 (10.3%)	46 of 68 (67.6%)	Not reported
300 Units Botulinum Toxin Type A	5 of 66 (7.6%)	41 of 66 (62.1%)	Not reported

Limitations and caveats (from the sponsor): First, this study was not designed to compare the effect of onabotulinum toxin A to placebo. Second, we assessed our primary outcome, treatment efficacy, at 3 months post-injection. The long-term safety of this product should also be evaluated.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 21791356Crawford ED, Hirst K, Kusek JW, Donnell RF, Kaplan SA, McVary KT, Mynderse LA, Roehrborn CG, Smith CP, Bruskewitz R. Effects of 100 and 300 units of onabotulinum toxin A on lower urinary tract symptoms of benign prostatic hyperplasia: a phase II randomized clinical trial. J Urol. 2011 Sep;186(3):965-70. doi: 10.1016/j.juro.2011.04.062. Epub 2011 Jul 24.
Individual participant dataSharing planned: Yes. Data are available at the NIDDK Central Repository https://repository.niddk.nih.gov/studies/mist2/?query=mist

Related trials for Benign Prostatic Hyperplasia

Recruiting
Clinical Study on Prostate Thermal Vapor Ablation Guided by MRI/TRUS Fusion Imaging
Benign Prostatic Hyperplasia (BPH)
Active, not recruitingPhase 4
Standard Versus Double Alpha Blockers Treatment for Symptomatic Benign Prostatic Obstruction
BPH (Benign Prostatic Hyperplasia)
RecruitingObservational study
ProVIDE Studies Post Exit Analysis
BPH With Symptomatic Lower Urinary Tract Symptoms
Recruiting
Learning Curve of Tri-lobar HoLEP Versus En-bloc HoLEP
Benign Prostatic Hyperplasia With Outflow Obstruction
RecruitingObservational study
Impact of Long-term Dutasteride Use on Perioperative Outcomes of HoLEP
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Reginald Bruskewitz, MD study chair

University of Wisconsin, Madison

7 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Jun 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Improvement in the AUA Symptom Score Index by 30% From Baseline Within the First 12 Weeks After Injection. (time frame: 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00451191, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Apr 2020.