Complementary and Alternative Medicine for Urological Symptoms(CAMUS)

Study Overview
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Brief Summary
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The CAMUS trial will test Saw palmetto in about 369 men. Men who decide to be part of the CAMUS trial will be given one out of two possible treatments at random. One out of every two men would get an inactive placebo treatment. One out of every two men would get Saw palmetto pills. This kind of scientific study is the best way to find out if the plant extracts really work to prevent men with benign prostatic hyperplasia (BPH) from getting worse. During the study, men will not know which of the two treatments they are assigned to. They will be followed very closely by a study team every 12 weeks to see how they are doing. Men in the CAMUS trial will be studied over 72 weeks. Tests and all medications needed as part of the study will be provided at no charge to the participant. Participants will be responsible for all other costs not associated with the study tests and medications. All information on study participants will be held in the strictest confidence and no one would have access to patient information other than the required authorized health care and research personnel.

Detailed Description
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The CAMUS trial is studying the outcomes using herbal therapy for benign prostatic hyperplasia (BPH). BPH is a common problem for older men. With BPH, the prostate grows larger. Over time, this growth can cause bothersome urinary symptoms. These symptoms can include frequent and/or urgent urination during the day or at night. Men with BPH can also have a weak urine stream, a stream that stops and starts, a feeling of not emptying the bladder all the way, and/or a need to strain to get urination started. BPH is NOT the same as prostate cancer. A number of natural products (extracts of different plants) seem to be able to reduce the bothersome symptoms of BPH with very few side effects over a few months. One of the plant extracts comes from the dwarf palm tree (Saw palmetto). The investigators do not know whether these plant extracts will reduce the symptoms of BPH over a longer period of treatment.

Official Title
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Complementary and Alternative Medicine for Urological Symptoms (CAMUS)

Conditions
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Urological

Intervention / Treatment
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* Drug: Saw Palmetto - first 24 weeks
* Drug: Placebo - first 24 weeks
* Drug: Saw Palmetto - weeks 24 - 48
* Drug: Placebo - weeks 24 - 48
* Drug: Saw Palmetto - weeks 48 - 72
* Drug: Placebo - weeks 48 - 72


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: To be eligible for the study, potential participants must meet all of the following eligibility criteria: Male at least 45 years of age. Peak urinary flow rate at least 4 ml/sec with a voided volume of at least 125 ml. AUA symptom score ≥ 8 and ≤ 24 at both screening visits. Voluntarily signed informed consent agreement prior to the performance of any study procedures. Exclusion Criteria: Potential participants that meet any of the following exclusion criteria will be excluded from the full-scale trial: Any prior invasive intervention for BPH. Phytotherapy for BPH or a 5-alpha reductase inhibitor within 3 months. Alpha blocker within one month. Reported allergic reaction to Serenoa repens. Taken phenylephrine, pseudoephedrine, tricyclic antidepressants, and anticholinergic or cholinergic medication within 4 weeks of the first screening visit, with the following exception: topical anticholinergic eye drops used for glaucoma. Taken an estrogen, androgen, or any drug producing androgen suppression, or anabolic steroids within 6 months. Known clinically significant renal impairment (i.e., creatinine greater than 2.0 mg/dl). Alanine aminotransferase(ALT)serum glutamic pyruvic transaminase(SGPT), aspartate aminotransferase(AST)serum glutamic oxaloacetic transaminase (SGOT) or gamma-glutamyltranspeptidase (GGT) value greater than 3 times the upper limit of normal in the clinical center lab at SV1.0; confirmed on a second measurement. Prothrombin time greater than 3 seconds above the upper limit of normal, or more than 3 seconds above the control value in the clinical center at SV1.0; confirmed on a second measurement. Electrocardiogram (ECG) reading at the clinical center at SV1.0 suggesting active ischemia or recent myocardial infarction until appropriate consultation confirms the absence of an acute coronary syndrome. Prostate-specific antigen (PSA) level greater than 10 ng/ml at the first screening visit. Requires the daily use of a pad or device for incontinence, or International Continence Society male incontinence symptom (ICSmaleIS) score >14 at screening. Unstable medical condition within the past 3 months. History or current evidence of carcinoma of the prostate or bladder, pelvic radiation or surgery, urethral stricture, or prior surgery for bladder neck obstruction. Active urinary tract disease or has undergone cystoscopy or biopsy of the prostate within one month prior to the first screening visit or has an imminent need for urologic surgery. Known primary neurologic conditions such as multiple sclerosis or Parkinson's disease or other neurological diseases known to affect bladder function. Documented bacterial prostatitis within the past year. Two documented independent urinary tract infections of any type in the past year. Known severe bleeding disorder or need for ongoing therapeutic anticoagulation with coumadin or heparin. Cancer, which is not considered cured (except basal cell or squamous cell carcinoma of the skin). A potential participant is considered cured if there has been no evidence of cancer within five years of randomization. A history of bladder cancer or prostate cancer is exclusionary whether the participant is considered cured or not. Unable to follow protocol directions due to organic brain or psychiatric disease. History of alcoholism or any other substance abuse, which, in the opinion of the investigator, would affect compliance with the protocol. Any serious medical condition likely to impede successful completion of the study.

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants will take one 320 mg placebo gelcap daily for 24 weeks one gelcap); followed by 640 mg daily for 24 weeks (two gelcaps) followed by 960 mg daily for 24 weeks (three gelcaps). | Drug: Placebo - first 24 weeks<br>* Participants will take one 320 mg chocolate-colored soft gelcaps containing a placebo for 24 weeks.<br>Drug: Placebo - weeks 24 - 48<br>* Participants will take 640 mg (2) chocolate-colored soft gelcaps containing a placebo for 24 weeks.<br>Drug: Placebo - weeks 48 - 72<br>* Participants will take 960 (3) mg chocolate-colored soft gelcaps containing a placebo for 24 weeks.<br>|
| Active Comparator: Saw Palmetto<br>Extract of Serenoa Repens 320 mg once daily for 24 weeks (one gelcap); followed by 640 mg daily for 24 weeks (two gelcaps) followed by 960 mg daily for 24 weeks (three gelcaps). | Drug: Saw Palmetto - first 24 weeks<br>* Participants will take one 320 mg chocolate-colored soft gelcaps containing a standardized saw palmetto fruit extract for 24 weeks.<br>Drug: Saw Palmetto - weeks 24 - 48<br>* Participants will take 640 mg (2) chocolate-colored soft gelcaps containing a standardized saw palmetto fruit extract for 24 weeks.<br>Drug: Saw Palmetto - weeks 48 - 72<br>* Participants will take 960 (3) mg chocolate-colored soft gelcaps containing a standardized saw palmetto fruit extract for 24 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean and Standard Deviation of the Participant American Urological Association (AUA)Symptom Score Between Baseline and Week 72 for CAMUS Participants. | The primary outcome was the mean difference in the AUA Symptom Score between baseline and 72 weeks between the saw palmetto and placebo groups. The AUA Symptom Score index is a seven item questionnaire assessing the frequency of lower urinary tract symptoms (LUTS). The questions are scored on a scale of zero to five, with zero being never, one to four being one to four accordingly, and five equaling five or more times. A Symptom Index is determined by adding the scores. The lowest possible score is 0 and the highest possible score is 35, which would represent the highest level of pain and discomfort. | Baseline to 72 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants Global Assessments of Improvement and Satisfaction at End of Study. | Participants' global assessments of improvement and satisfaction at the end of the study. Likert scales were transformed to a 0 - 100 scale. The lowest possible score is 0 and the highest possible score is 100, which would reflect better outcomes. | Baseline to 72 weeks | 
| Benign Prostate Hyperplasia (BPH) Impact Index Score | The mean difference in the BPH Impact Index score from baseline to 72 weeks in participants that were included in the modified intention to treat analysis. The BPH Index Score is a self administered 4 item index. Three questions are scored on a scale from 0 to 3, with zero being none, one being only a little, two being some, and three being a lot. One question is scored on a scale from 0 to 4, with zero being none of the time, one being a little of the time, two being some of the time, three being most of the time, and four being all of the time. The lowest possible score is 0 and the highest possible score is 13, which would represent the greatest dysfunction. | Baseline to 72 weeks | 
| International Prostate Symptom Score Quality of Life (IPSS QOL) Score | The mean difference in the IPSS Quality-of-Life Question from baseline to 72 weeks in participants that were included in the modified intention to treat analysis. The IPSS Quality-of-Life Question is an additional question to the AUA Symptom Score. The self administered question is scored on a scale from 0 to 6, with zero being delighted, one being pleased, two being mostly satisfied, three being mixed-about equally satisfied and dissatisfied, four being mostly dissatisfied, five being unhappy, and six being terrible. The lowest possible score is 0 and the highest possible score is 6, which would represent the greatest dysfunction. | Baseline to 72 weeks | 
| American Urological Association(AUA) Nocturia Item | The mean difference in the nocturia item of the AUA Symptom Score from baseline to 72 weeks in participants that were included in the modified intention to treat analysis. The nocturia item is a self administered question from the AUA Symptom Score Index that assesses the number of times a participant typically gets up to urinate from the time he goes to bed at night until the time he gets up in the morning. The question is scored on a scale of zero to five, with zero being none, one being one time, two being two times, three being three times, four being four times, and five being five or more times. The lowest possible score is 0 and the highest possible score is 5, which would represent the highest level dysfunction. | Baseline to 72 weeks | 
| Peak Uroflow | The mean difference in the participants' peak uroflow from baseline to 72 weeks in the modified intention to treat analysis. The peak uroflow was measured in milliliters/seconds. The higher units indicated greater dysfunction. | Baseline to 72 weeks | 
| Post-void Residual | The mean difference in the participants' post-void residual from baseline to 72 weeks in the modified intention to treat analysis. The post-void residual was measured in milliliters. The higher units indicated greater dysfunction. | Baseline to 72 weeks | 
| Prostate Specific Antigen (PSA) Level | The mean difference in the PSA level from baseline to 72 weeks in the modified intention to treat analysis. The PSA level was measured in nanograms/milliliters. The higher units indicated greater dysfunction. | Baseline to 72 weeks | 
| International Index of Erectile Function (IIEF)Scale Score. | The mean difference in the IIEF score from baseline to 72 weeks in participants that were included in the modified intention to treat analysis. The IIEF is a multidimensional scale for assessment of erectile dysfunction. The six item self administered questionnaire is scored on a scale from 0 to 5, with zero being no sexual activity, one being never or almost never, two being a few times (much less than half the time), three being sometimes (much less than half the time), four being most times (much more than half the time), and five being always or almost always. The lowest possible score is 0 and the highest possible score is 30, which represents less dysfunction. | Baseline to 72 weeks | 
| Male Sexual Health Questionnaire - Ejaculatory Domain (MSHQ-EjD) Scale Score. | The mean difference in the MSHQ-EjD from baseline to 72 weeks in participants that were included in the modified intention to treat analysis. The MSHQ-EjD scale is used for the assessment ejaculatory dysfunction (EjD). The MSHQ-EjD consists of four self administered questions. Three of the items are scored on a scale from 0 to 5, with zero being all the time, one being most of the time, two being some of the time, three being a little of the time, four being none of the time, and five being no sexual activity. The fourth item is scored on a scale of 1 - 5, with one being not at all bothered, two being a little bit bothered, three being moderately bothered, four being very bothered, and five being extremely bothered. The lowest possible score is 0 and the highest possible score is 20, which represents the highest level of dysfunction. | Baseline to 72 weeks. | 
| International Continence Society Male Incontinence Symptom (ICSmale IS) Score | The mean difference in the ICSmaleIS score from baseline to 72 weeks in participants that were included in the modified intention to treat analysis. The six item self administered questionnaire is scored on a scale from 0 to 4, with zero being never, one being occasionally, two being sometimes, three being most of the time, and four being all of the time. The lowest possible is 0 and the highest possible score is 24, which represents the the highest level of dysfunction. | Baseline to 72 weeks | 
| Jenkins Sleep Scale Score | The mean difference in the Jenkins Sleep Dysfunction score from baseline to 72 weeks in participants that were included in the modified intention to treat analysis. Jenkins Sleep Dysfunction score is used to assess sleep dysfunction. The four item self administered questionnaire is scored on a scale from 0 to 5, with zero being not at all, one being 1 -3 days, two being 4 - 7 days, three being 8 - 14 days, four being 15 - 21 days, and five being 22 - 31 days. The lowest possible score is 0 and the highest possible score is 20, which represents the highest level of dysfunction. | Baseline to 72 weeks | 
| NIH-Chronic Prostatitis Symptom Index (NIH-CPSI) Pain Scale | The mean difference in the NIH-Chronic Prostatitis Symptom Index (NIH-CPSI) Pain Scale score from baseline to 72 weeks in participants that were included in the modified intention to treat analysis. The NIH-Chronic Prostatitis Symptom Index (NIH-CPSI) Pain Scale is a four item self administered questionnaire. Three of the four items are scored on a scale from 0 - 1, with zero being no and one being yes. The fourth item is scored on a scale from 0 - 10, with zero being no pain and ten being pain as bad as you can imagine. The lowest possible score is 0 and the highest possible score is 21, which represents the highest level of pain. | Baseline to 72 weeks | 
| NIH-Chronic Prostatitis Symptom Index (NIH-CPSI) Urinary Symptom Scale | The mean difference in the NIH-Chronic Prostatitis Symptom Index (NIH-CPSI) urinary symptom scale from baseline to 72 weeks in participants that were included in the modified intention to treat analysis. The NIH-Chronic Prostatitis Symptom Index (NIH-CPSI) urinary symptom scale consists of two self administered questions. The questions are scored on a scale from 0 - 5, with zero being not at all, one being less than 1 time in 5, two being less than half the time, three being about half the time, four being more than half the time, and five being almost always. The lowest possible score is 0 and the highest possible score is 10, which represents the highest level of dysfunction. | Baseline to 72 weeks | 
| NIH-Chronic Prostatitis Symptom Index (NIH-CPSI) Quality of Life (QOL)Scale | The mean difference in the NIH-Chronic Prostatitis Symptom Index (NIH-CPSI) Quality of Life (QOL) scale from baseline to 72 weeks in participants that were included in the modified intention to treat analysis. The NIH-Chronic Prostatitis Symptom Index (NIH-CPSI) Quality of Life (QOL) scale consists of three self administered questions. Two of the questions are scored on a scale of 0 - 3, with zero being none, one being only a little, two being some, and three being a lot. The third question is scored on a scale of 0 -6, with zero being delighted, one being pleased, two being mostly satisfied, three being mixed (equally satisfied and dissatisfied), four being mostly dissatisfied, five being unhappy, and six being terrible. The lowest possible score is 0 and the highest possible score is 12, which represents the highest level of dysfunction. | Baseline to 72 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Serenoa repens, Urological symptoms, hyperplasia, BPH