|ORIGINAL RESEARCH REPORT
|Year : 2014 | Volume
| Issue : 1 | Page : 2-6
The efficacy of procin-x and celloid-s in the management of benign prostatic enlargement
KH Tijani1, MK Adegoke2, EA Jeje1, KI Okolie2, RW Ojewola1, MA Ogunjimi1
1 Department of Surgery, Section of Urology, Lagos University Teaching Hospital, Surulele, Lagos, Nigeria
2 Department of Chemical Pathology, Lagos University Teaching Hospital, Surulele, Lagos, Nigeria
|Date of Web Publication||21-Jul-2014|
K H Tijani
Department of Surgery, Section of Urology, Lagos University Teaching Hospital, Surulere, Lagos
Source of Support: None, Conflict of Interest: The authors however
did not receive any honorarium from the manufacturers of Procin-X
Background and Objective: Despite a decent efficacy and safety profile, α1 - blockers (A1B) and the 5α - reductase inhibitors (5ARI), the conventional drugs used in the treatment of the symptoms of Benign Prostatic Hyperplasia (BPH), are commonly associated with adverse effects including sexual dysfunction and postural hypotension. Phytotherapy for the treatment BPH symptoms has been used for centuries. However, scientific data on their efficacy are sparse. Procin-X and Celloid-S (PC) are powdered plant material products with acclaimed anti- BPH properties. This study assessed their usefulness in the management of BPH. Materials and Methods: This was a single blind, randomized, placebo-controlled study conducted at our hospital involving 80 patients (divided in to 2 equal groups) with the clinical diagnosis of BPH. The study group were given PC while the controls were given multivitamin Capsules daily for a period of 14 weeks. All patients were evaluated at intervals for severity of symptoms, flow rates, prostate size, prostate specific antigen (PSA) and possible adverse effects including erectile function. Test of significance between the means was done using the Students Paired t-test. A P < 0.05 was considered significant. Results: At the end of 14 weeks there was an reduction in symptom score by 5.7 and 1.6 in subjects and controls respectively (P < 0.05) and an increase in flow rate by 4.0mls/s and 1.1mls/s respectively (P < 0.05). There was a 60% and 14% reduction in PSA in the subjects and control respectively. There was also statistically significant increase in the erection score in the subjects. Conclusion: PC appear to be effective and in the management of the symptoms of BPH. The positive effects of PC on erectile function may however give them an advantage over the A1B and 5ARI drugs while the reduction in PSA may also give it a role in chemoprevention of prostate cancer. A large scale cohort study is needed to confirm these findings.
Keywords: Celloid-S, phytotherapy, procin-X, prostate
|How to cite this article:|
Tijani K H, Adegoke M K, Jeje E A, Okolie K I, Ojewola R W, Ogunjimi M A. The efficacy of procin-x and celloid-s in the management of benign prostatic enlargement. J Clin Sci 2014;11:2-6
|How to cite this URL:|
Tijani K H, Adegoke M K, Jeje E A, Okolie K I, Ojewola R W, Ogunjimi M A. The efficacy of procin-x and celloid-s in the management of benign prostatic enlargement. J Clin Sci [serial online] 2014 [cited 2019 May 22];11:2-6. Available from: http://www.jcsjournal.org/text.asp?2014/11/1/2/137240
| Introduction|| |
Benign enlargement of the prostate is almost always synonymous with the normal male aging process.  Patients commonly present with lower urinary tract symptoms (LUTS). The etiology and pathogenesis of benign prostatic enlargement also commonly called benign prostatic hyperplasia (BPH) is still not clearly understood. Apart from age, the other obligatory factor for the development of BPH is androgen dihydrotestosterone (DHT) since men born with a deficiency of 5α-reductase enzyme, which converts testosterone to DHT, do not develop BPH. , As men age, the circulating testosterone decreases while the number of androgen receptors in the prostate increases, leading to an increase is prostatic size and subsequence obstruction in bladder outflow. , The mechanical compression of the prostatic urethra, also called the static component, and the hyper-contractility of the α1 -receptor sensitive pre-prostatic smooth muscles, also called the dynamic component, are the main mechanisms by which BPH causes bladder outflow obstruction (BOO). ,,
Therapy is needed in BPH either to relieve symptoms or to stop the progression of complications. Presently, the recommended practice is to manage non-complicated cases with initial pharmacotherapy.  The currently available drugs are α1 blockers (A1B) and the 5α-reductase inhibitors (5ARI). Complicated or more severe cases are managed by different forms of surgical intervention with varying degrees of success and complications including mortality. The common side effects of A1B are postural hypotension, dizziness, and ejaculatory dysfunction, whereas 5ARI are associated with reduced libido and erectile dysfunction. , These problems have continually led to interests in alternative treatments.
The drugs procin-X and celloid-S (PC) are plant extracts. The plants had been claimed by the locals (and manufacturers of PC) to have medicinal properties in the treatment of various prostatic disorders. Coker et al., had also reported in vitro anti-sickling properties of celloid-S.  In this study, we tried to assess some of these claims on the treatment prostatic disorders.
| Materials and Methods|| |
This was a single blind, randomized, placebo-controlled study conducted at the Lagos University Teaching Hospital (LUTH). The study was approved by the institution research and ethics board. Informed consent was taken from each participant
Sample size calculation
Assuming a 15% withdrawal, a 30% change in end-point, a P value of statistical significance of 0.05 at 80% power, the required final sample size was calculated using the standardized normogram for sample size calculation. , The minimum number for analysis was calculated at 26 for each arm, and the minimum number of subjects to be recruited was calculated at 70 (35 for each arm).
All patients diagnosed with clinical BPH who provided informed consent were included. Clinical BPH was defined as the presence of lower urinary tract symptoms (LUTS) in a patient with an enlarged prostate detected by digital rectal examination or imaging studies.
All patients with disorders known to produce LUTS, e.g. uncontrolled diabetes mellitus, bladder stones, suspected cancer of the prostate, neurogenic bladder, urethral stricture, bladder neck stenosis, and patients with complicated BPH, e.g., acute retention, overflow incontinence, recurrent bleeding, and renal failure, were excluded.
Botanical identification and quality were assessed by National Agency for Food and Drug Administration and Consumption (NAFDAC) approved pharmacologists and toxicologists. The drugs have also been licensed by NAFDAC for human consumption and clinical practice.
The drugs procin-X and celloid-S are packaged separately in 500-mg capsular forms. Celloid-S contains extracts from species of Alcornia (cordifolia, floribunda, laxifolia, and hirtellla) while procin contains extracts from Setaria species (barbata, longiseta, megaphylla, and pallidefusca). The stability of the drug was tested with a shelf life of 3.1 years.
Adverse effects and withdrawals
All adverse effects observed or reported by patients were noted. For patients who decided to drop out, efforts were made to ascertain the reason for the drop out. Failure to take less than 80% of medication was regarded as a treatment failure or withdrawal.
The primary efficiency end points were the international prostate symptom score (IPSS) score, Peak flow rate (Q max ), Quality of life (Qol) score, post-void residual urine (PVR), and prostatic volume on pelvic ultrasonography; the secondary efficiency end points were the International Index of Erectile function (IIEF-5) questionnaire score, electrolytes urea, and creatinine prostate specific antigen (PSA), serum testosterone, full blood count, and liver function tests.
Eighty subjects were randomized into two groups of 40 each, consisting of the placebo and drug (PC) groups. The randomization was done by sequential opening of sealed opaque envelopes containing the random group allocation. This was generated by one of the authors, also a statistician (KIO), using a block randomization method (with a block size of 8 to ensure equal sample size) and a table of random numbers. The envelopes were opened by the principal investigator (KHT) in a sequence as each participant entered the study and the group subsequently allocated.
Drug administration and follow up
Each subject was given two capsules of procin-X twice daily and two capsules of celloid-S twice daily, while each control was given 200 mg of multivitamin capsules once daily. The patients were evaluated as above at pre-treatment and re-evaluated at 2, 6, 10, and 14 weeks.
Statistical analysis was done using the SPSS version 16 software. Test of significance between the means was done using the Students Paired t-test. A P < 0.05 was considered significant
| Results|| |
A total of 40 patients were recruited for each arm with five and 13 withdrawals in the PC and control groups, respectively. No improvement in symptoms was the reason given by four and 11 patients of the PC and control groups, respectively. The remaining patients gave no reasons. As a result, data of 62 patients were available for analysis [Table 1].
Statistically significant differences in IPSS score between the two groups were noticed as from two weeks. At the end of 14 weeks, there was a reduction in IPSS score of 5.7 and 1.6 in the PC and control groups, respectively (P < 0.05) [Table 2]. Approximately 37% and 15% of the PC and control groups, respectively, had more than 50% improvement in symptom score while 29% and 52% of the PC and control groups, respectively, had less than 25% improvement [Table 3]. There was an increase in peak flow rates by 4 ml/s and 1.1 ml/s in the PC and control groups, respectively, at the end of 14 weeks [Table 4].
At the end of 14 weeks, there was a reduction in PVR volume (PVRV) to 38 ml and 86.4 ml in the PC and control groups, respectively (P < 0.05) whereas the IIEF-5 increased by 4 in the PC group and reduced by 1.5 in the control group [Table 5]. There was a decline of PSA in the two groups but the decline was more in the PC group (P < 0.05) [Figure 1].
| Discussion|| |
BPH is commonly divided in to three types-microscopic BPH, which refers to the proliferation of cellular and stromal contents of the prostate; macroscopic BPH, which refers to the findings of an enlarged prostate on physical or radiological evaluation; and clinical BPH, which refers to the presence of LUTS attributable to an enlarged prostate. In clinical practice, the term BPH is generally synonymous with clinical BPH.
The components of LUTS are grossly divided into irritative (or storage) symptoms or obstructive (or voiding) symptoms and are usually graded using the IPSS. A patient with a score of less than 8 is regarded as having mild symptoms, 8-19 as moderate, and 20-35 as severe. ,,
The main indication for the drug treatment of BPH is to alleviate these symptoms. At the end of 14 weeks, PC was able to reduce the average IPSS score by 5.7 compared with 1.6 for the placebo, corresponding to a reduction of 32.4% and 10.1%, respectively [Table 2]. With 37.1% showing more than 50% decrease in symptom score and 71.4% showing more than 25% improvement in score, PC has comparable efficacy with established A1RB drugs doxazosin and terrazosin that have been reported to cause an IPSS reduction of 5.8, with 69% of the patients showing more than 30% improvement in symptom score  [Table 3]. A recent study in our environment using 8 mg of doxazosin, however, revealed a 44.4% reduction in IPSS.  However, only 18 patients were analyzed in that study, and there were no control subjects. The effect of PC was also significantly better than finasteride-the most extensively studied androgen suppressant, which causes only 21% reduction in symptoms score at the end of one year. 
Many other studies have also compared combination therapy of an α blocker and an androgen suppressant with conflicting results. While some showed a higher reduction in the rate of disease progression in patients on combination therapy, others did not. 
With a significant reduction in PVRV and a 4-ml/s increase in peak flow rate, the efficacy of PC in improving urinary flow appears comparable with a combination of doxazosin and finasteride therapy , [Table 4] and [Table 5].
Even though PC appear to be as good as a combination of an A1RB and 5ARI, the mechanism of action is unknown. Most patients noticed a response within one week of commencement of the drugs indicating that a reduction in prostate size was not the likely mechanism. Likewise at the end of 14 weeks, there was no statistically significant difference in the size of the prostate between the PC and control groups [Table 5]. This may, however, be due to the relatively short duration of the study as it is possible that long term usage may reveal a significant reduction in size.
There are two established pathways of managing symptoms of BPH. One way is to block the androgen receptors by using 5ARI leading to a regression in the size of the prostate, and the other is to use an A1B that relaxes the smooth muscles of the bladder neck. Both drugs, however, affect sexual function, with the former commonly causing erectile dysfunction and the latter causing ejaculatory dysfunction thereby making them unattractive to sexually active men. Postural hypotension and dizziness are also common.
While the efficacy of PC appears to be as good as the conventional combination therapy of a 5ARI and A1B, it appears to have key advantages over the conventional drugs. Known side effects of reduced libido, erectile dysfunction, hypotension, and dizziness common to a combination therapy were absent in this study. Apart from the absence of these side effects, there was an average increase of 4 in the IIEF-5 score of the patients on PC while there was a reduction of 1.5 in the control [Table 5]. In total, 54% of the patients with IIEF-5 score of less than 21 reported an improvement in score compared with 18% for placebo [Table 5]. Psychological reasons due to the associated improvement in LUTS may be a factor. However, other drugs like finasteride and dutasteride are known to improve LUTS and still cause erectile dysfunction. It is also possible that PC, like many of the so-called herbal preparations in our environment, may have aphrodisiacal effects without increasing the serum testosterone as there was no statistically significant difference in the starting and final serum testosterone between the PC and control groups [Table 5].
|Table 2: Effect of procin-X and celloid-S on the mean international prostate symptom score |
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|Table 3: Procin-X and celloid-S and the percentage change in international prostate symptom score |
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|Table 4: Effect of procin-X and celloid-S on the mean peak flow rate (Q max) |
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|Table 5: Effect of procin-X and celloid-S on radiological, biochemical, and clinical investigations |
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Another finding of note in this study was that there was a 41.2% and 59.4% reduction in the average prostate specific antigen (PSA) of the patients on PC at 6 weeks and 10 weeks, respectively. This was statistically significant when compared with the control group with reductions of 12.7% and 15.9%, respectively [Figure 1]. While the relevance of this in the management of BPH is not clear, the drug may also be able to find a place in the chemoprevention for prostate cancer as 5ARI drug finasteride-known to reduce serum PSA-has now been licensed for the chemoprevention of prostate cancer. , However, unlike finasteride, PC tend to improve erectile function rather than impairing it. There is presently no known drug or drug combination that does this. A large scale multicentre cohort study will, however, be needed to determine the usefulness of PC in this regard as the confirmation of these effects could have significant implications on urological practice.
Despite these advantages, the use of PC, however, has some major challenges. PC are packaged as two different drugs to be used together, with each one containing a variety of chemical compounds including free fatty acids and sitesterols. Neither the exact active components nor the mechanisms of action of these drugs are known. Attending to these issues may also solve the problem of multiple daily dosing as the patient needs to swallow at least eight capsules of PC a day. This may adversely affect compliance and is a disadvantage when compared with 5ARI or A1B, which have once daily regimens. Likewise, neither the most effective duration of therapy nor the effects of the long term usage of PC are presently known.
In conclusion, PC appear to be effective and in the management of LUTS caused by BPH. This efficacy appears to match that of a combination therapy of a 5ARI and A1B. The key advantages of PC include the absence of known side effects, the apparent improvement of erectile function with a simultaneous reduction in PSA, and no significant effect on serum testosterone. It may, thus, also find additional role in the chemoprevention of prostate cancer. A large multicenter double blind study is, however, needed to confirm these findings.
| Acknowledgement|| |
We would like to thank Ormed Supreme Option Ltd. for supplying free samples of procin-X and celloid-S, the laboratory kits, and offsetting the cost of ultrasound scanning and uroflowmetry; all the resident doctors in Urology who assisted in data collection; and the authorities of the Lagos University Teaching Hospital.
| References|| |
|1.||Roehrborn GG. Benign prostatic hyperplasia. Aetiology, pathophysiology, epidermiology and natural history. In: Wein J, Kavouss LR, Partin AW, Norick AC, Peters CA, editors. Campbell's Urology. 10 th ed. Philadelphia: Elsevier-Saunders; 2012. p. 2570-612. |
|2.||Naderi N, Mochtar CA, de la Rosette JJ. Real life practice n the management of benign prostatic hyperplasia. Curr Opin Urol 2004;14:41-4. |
|3.||Presti JC, Kane CJ, Katsuko. Neoplasm of the Prostate. In: Tanagho EA, Mcaninch JW, editors. Smiths General Urology. New York: Mcgraw-Hill; 2008. p. 348-75. |
|4.||Lepor H, Jones K, Williford W. The mechanism of adverse events associated with terazosin: An analysis of the veterans affairs cooperative study. J Urol 2000;163:1134-7. |
|5.||Coker HA, Kehinde MO, Temiye EO, Banjo AA, Elesha SO, Sofola OA, et al. Does re-hydration necessarily imply re-oxygenation in sickling reversal: The Gardos phenomenon revisited. A case for Celloid-S herbal remedy. J Pharm Sci Pharm Pract 2006;8:122-31. |
|6.||Jeyaraman R, Patki PS. Clinical evaluation of efficacy and safety of a herbal formation in benign prostatic hyperplasia: A single blind, randomised, placebo-controlled study. Open J Urol 2012;2:157-13. |
|7.||Whitley E, Ball J. Statistics review 4: Sample size. Crit Care 2002;6:335-41. |
|8.||Jeje EA, Dogunro AS, Ogunjimi MA, Tijani KH. Efficacy and safety of dixazosin (cadura) in the management of benign prostatic hyperplasia. Niger J Surg 2011;17:55-9. |
|9.||Kirby RS, Roerhborn C, Boyle P, Bartsch G, Jardin A, Cary MM, et al. Prospective European Doxazosin and Combination Therapy Study Investigators. Efficacy and tolerability of doxazosin and finasteride, alone or in combination, in treatment of symptomatic benign prostatic hyperplasia: The prospective European doxazosin and combination therapy (PREDICT) Trial. Urology 2003;61:119-26. |
|10.||Droggrell SA. Present and future pharmaco-therapy for benign prostatic hyperplasia. Drugs Future 2002;27:973-86. |
|11.||Thompson IM, Goodman PJ, Tangen CM, Lucia MS, Miller GJ, Ford LG, et al. The influence of finasteride on the development of prostate cancer. N Engl J Med 2003;349:215-24. |
|12.||Thompson IM, Klein EA, Lippman SM, Coltman CA, Djavan B. Prevention of prostate cancer with finasteride: A U.S./European Perspective. Eur Urol 2003;44:650-5. |
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]