Crila® Herbal Supplement Reduces Lower Urinary Tract Symptoms in Latino Men

Bernard W. Somers1, Betsy Singh2, Laura J. Camacho Choza3, Pablo F. Gonzalez Limon3, Francisco Gomez Regalado3, Mark Scholz4, Nadina Jose5

1Department of Medicinal Chemistry, Rutgers University New Brunswick, NJ, 2BRCG Medical Research Group, Midlothian, VA, 3PanAmerican Clinical Research Group, Mexico, 4Prostate Oncology Specialists, California; Medical Director, Prostate Cancer Research Institute of Los Angeles, California, 5Department of Health Informatics, Rutgers University Newark, NJ

Abstract

Lower urinary tract symptoms (LUTS) are commonly experienced by men as they age, affecting 56% of men ages 50-79 and 70% of men ages 80-89. A study of 3,301 participants published in Urology indicates black and Hispanic men have the greatest incidence of LUTS1. Previously, a single group, open-label study at 3 hospitals in Vietnam was performed over 2 months to assess Crila® herbal supplement in 189 men. 89.2% showed a beneficial response on the American Urological Association (AUA) Symptom Score Survey (p < 0.001). A prospective, open-label dietary supplement clinical study was approved by 2 Ethics Committees in Mexico to study oral Crila® herbal supplements (Crinum latifolium L var. crilae Tram & Khanh) in 49 men with LUTS. Crila® was taken orally for 90 days in Guadalajara and Querétaro, Mexico. Every 30 days symptom severity was quantified using the AUA Symptom Score Survey to determine the benefits of Crila®. 88% of the men showed improvement in their LUTS after study completion while significant improvement was observed from Day 0 to each subsequent visit, and from Day 30 to Day 90 (p = 0.006). When comparing the Screening/Baseline Visit to all 3 following visits, we observe a significant decrease (p < 0.001) in total prostate score on the AUA Symptom Score Survey.

Background

LUTS are commonly experienced by men as they age1. Over-the-counter plant extracts, such as saw palmetto (Serenoa repens), have been used in an attempt to address LUTS in men2. However, studies examining the efficacy of these over-the-counter plant extracts have been inconclusive3 4. The genus Crinum, including C. latifolium, has been used as a traditional medicinal herb in Asia and around the world. In 2005, an unpublished clinical study of 189 men examined the use of Crila® for prostate health. Of 157 completers, 89.2% showed a beneficial response on the AUA Symptom Score Survey (p < 0.001) with no significant changes in vital signs, liver enzymes, creatinine, or leucocytes. 20 patients (12.73%) experienced possibly attributable mild transient side effects, primarily gastrointestinal (17 subjects), dizziness (4), rash (2) and insomnia (1). A study conducted by the Vietnam Ministry of Health and National Institute of Gerontology reiterated the beneficial safety profile of C. latifolium extract as a well-tolerated herb with minimal side effects and suggests that it can reduce the severity of LUTS in men as early as two weeks after initiation5. 

Methods

This study is a two-center, prospective, open-label study in men with lower urinary tract symptoms (LUTS) who received 4 to 10 capsules (depending on body weight) of C. latifolium extract (Crila®) for 3 months (Table 1, Table 2). This study was conducted in 2 university affiliated centers in Mexico. The study’s primary endpoint was designed to evaluate the impact of oral Crila® capsules on LUTS as assessed by the AUA Symptom Score survey (Figure 1). Subjects who met all inclusion and none of the exclusion criteria were evaluated throughout the study. 49 subjects completed the study. Subjects completed procedures as detailed in Table 1. A subject’s total study duration comprised up to 90 days from screening (Day 0) through conclusion of the Final Visit (Day 90).

Table 1. Study Schedule Over 90 Days

Figure 1. AUA Symptom Score Survey

Table 2. Dosing and Administration

Inclusion criteria:

Male subjects > 40 years of age; BMI < 30; Score of >10 on AUA Symptom Score Survey; Able and willing to return to the clinic for all study procedures; Able and willing to provide informed consent.

Exclusion criteria: 

BMI > 30; Score of < 10 on AUA Symptom Scale; Previous history of cancer; History or presence of myocardial infarction or stroke; Blood pressure > 165 diastolic or > 95 systolic; Clinically significant pulmonary, cardiac, gastroenterologic, neurologic, renal, musculoskeletal, rheumatologic, metabolic, neoplastic, or endocrine disease or any clinically significant abnormalities on physical examination, medical history, or vital signs as judged by the Investigator; Concurrent administration of St. John’s wort (Hypericum perforatum), black cohosh (Actaea racemosa), maca (Lepidium meyennii), red clover (Trifolium pratense), aromatase inhibitors, or SSRIs for previous 3 months; History of deep vein thrombosis, thrombophlebitis or thromboembolic disorder; Subjects with a significant acute condition, or any other condition that, in the opinion of the Investigator, might interfere with the evaluation of the study objectives; Currently taking any of the following medications: corticosteroids (oral replacement of ≤ 5 mg/day prednisolone, inhaled and topical corticosteroids are allowed), immunomodulatory treatments, or any prescription that, in the opinion of the Investigator; Current alcohol or substance abuse that, in the opinion of the investigator, would interfere with adherence to study requirements; Participation in any clinical study with an experimental medication where the last dose was within 5 half-lives or 30 days (whichever is longer) of enrollment in the current study, or participation in any study with an experimental device within 30 days of enrollment in the current study; uncontrolled diabetes in the Investigator’s opinion; dementia or significant signs of compromised cognitive ability.

Results

The mean total score for each of the 4 visits for N = 49 subjects who completed the study is illustrated in Figure 2 and listed in Table 3. When compared to the Baseline Visit 1, subsequent visits have a significantly lower total score on AUA survey (p < 0.001, Figure 2, Table 4) suggesting Crila® continually reduced LUTS symptoms over the entire course of the regimen. When comparing the p-vaue of Visit 2 to Visit 3 (p = 0.695) and the p-value of Visit 3 to Visit 4 (p = 0.126) a trend toward significance was observed suggesting a longer regimen may provide a more clinically meaningful effect. One reason for the observed trend is it may take Crila® up to 90 days to elicit a significant physiological response. Additionally, when comparing each of the visits, Table 4 suggests there is no significant difference in total score when comparing Visit 2 to Visit 3 (p = 0.695). Total score of Visit 2 is significantly lower than Baseline Visit 1 (p = 0.001) and significantly higher than Final Visit 4 (p = 0.006). There is no significant difference in total score of Visit 3 and Final Visit 4 (p = 0.126). 28 of 49 (57%) subjects completed the study in the “Mild” symptom score range (Figure 3, Table 5). Of the 11 subjects who started “Severe,” 4 completed the study in the “Mild” symptom score range, 5 completed the study in the “Moderate” symptom score range (Figure 4, Table 5).

Figure 2. AUA Symptom Score Survey Results

Figure 3. AUA Symptom Score Index Results 

Figure 4. AUA Symptom Score Index Sub-score Analysis

Conclusion

Crila® herbal supplement is a clinically effective botanical product in reducing LUTS symptoms of male subjects. According to the data, symptoms are continually reduced over the entire course of the 90-day regimen and the extent to which they reduce increases with time. A recommendation for a longer duration study of 6-12 months would indicate if symptoms continue to improve over a longer course of time and if/when a symptom plateau is observed. This longer duration study will provide information to inform an initial dosing schedule and a maintenance dosing schedule in males with LUTS.

For further information:

Bernard W. Somers: bernard.somers@rutgers.edu
Nadina Jose MD: ncj26@rutgers.edu