Cyclooxygenase-2 (COX-2) Inhibitor Reduces Serum Prostatic Specific Antigen (PSA) Levels

NCT01678313 | Completed Phase 2 Results

• 1 other identifier: TCGHUROL004
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

Brief Summary

To investigate the therapeutic effect and safety of celecoxib adding on doxazosin and the potential predictive value of the absence of prostate cancer in the treatment of patients with LUTS/BPH and an elevated serum PSA level. Patients who meet all eligible requirements for entry into the study will be randomized into one of the two treatment groups for 3 months in 2:1 ratio as shown below:

1. 1.Doxazosin 4 mg daily plus celecoxib 200 mg every day (QD)
2. 2.Doxazosin 4mg every day (QD)

Conditions

Benign Prostatic Hyperplasia

Keywords

Benign prostatic hyperplasia (BPH); Lower urinary tract symptoms (LUTS); Prostatic specific antigen (PSA); Cyclooxygenase-2 (COX-2)

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in the Serum Prostate Specific Antigen (PSA) Level

  Efficacy: Change from Baseline in the serum PSA level from baseline and 3 months Change = Month 3 minus Baseline value

  Baseline and 3 months after initial treatment

Secondary Outcomes (5)

• Change From Baseline in the Void Volume (VV)

  Baseline and 3 months after initial treatment

• Change From Baseline in the Maximum Flow Rate (Qmax)

  Baseline and 3 months after initial treatment

• Change From Baseline in the IPSS Subscore (IPSS Voiding) Questionnaires

  Baseline and 3 months after initial treatment

• Change From Baseline in the IPSS Subscore (IPSS Storage) Questionnaires

  Baseline and 3 months after initial treatment

• Change From Baseline in the International Prostate Symptom Score (IPSS) Questionnaires

  Baseline and 3 months after initial treatment

Study Arms (2)

Study group

EXPERIMENTAL

Doxazosin 4 mg daily plus celecoxib 200 mg every day (QD)

Drug: Doxazosin 4 mg daily plus Celecoxib 200 mg every day (QD)

Control group

EXPERIMENTAL

Doxazosin 4 mg every day (QD)

Drug: Doxazosin 4 mg every day (QD)

Interventions

Doxazosin 4 mg daily plus Celecoxib 200 mg every day (QD) DRUG

Study group

Also known as: Doxazosin 4 mg, Celecoxib 200 mg

Study group

Doxazosin 4 mg every day (QD) DRUG

Control group

Also known as: Doxazosin 4 mg

Control group

Eligibility Criteria

• Age: 40 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male adults aged ≥ 40 years with LUTS/BPH, IPSS ≥ 8
• Free of active urinary tract infection
• Free of neurogenic voiding dysfunction
• No history of previous prostate biopsy within 6 months
• No treatment of BPH by alpha-blocker or 5-alpha-reductase inhibitor within 6 months
• Patient or his legally acceptable representative has signed the written informed consent form

You may not qualify if:

• Patients with severe cardiopulmonary disease and such as congestive heart failure, arrhythmia, poorly controlled hypertension, not able to receive regular follow-up
• Patients with acute r chronic urinary retention and urodynamically proven detrusor underactivity
• Patients with postvoid residual \> 250 mL
• Patients have laboratory abnormalities at screening including:
• Aspartate aminotransferase (AST) \> 3 x upper limit of normal range
• Alanine aminotransferase (ALT) \> 3 x upper limit of normal range
• Patients have abnormal serum creatinine level \> 2 x upper limit of normal range
• Patients with any other serious disease or condition considered by the investigator not suitable for entry into the trial
• Patients participated investigational drug trial within 1 month before entering this study

Sponsors & Collaborators

• Buddhist Tzu Chi General Hospital: lead

Study Sites (1)

Buddhist Tzu Chi General Hospital

Hualien City, 970, Taiwan

Location

Related Publications (13)

• Liu HT, Kuo HC. Urinary nerve growth factor levels are increased in patients with bladder outlet obstruction with overactive bladder symptoms and reduced after successful medical treatment. Urology. 2008 Jul;72(1):104-8; discussion 108. doi: 10.1016/j.urology.2008.01.069. Epub 2008 Apr 8.

  PMID: 18400272 BACKGROUND

• St Sauver JL, Sarma AV, Jacobson DJ, McGree ME, Lieber MM, Girman CJ, Nehra A, Jacobsen SJ. Associations between C-reactive protein and benign prostatic hyperplasia/lower urinary tract symptom outcomes in a population-based cohort. Am J Epidemiol. 2009 Jun 1;169(11):1281-90. doi: 10.1093/aje/kwp085. Epub 2009 Apr 24.

  PMID: 19395697 BACKGROUND

• Andersson KE. LUTS treatment: future treatment options. Neurourol Urodyn. 2007 Oct;26(6 Suppl):934-47. doi: 10.1002/nau.20500.

  PMID: 17696154 BACKGROUND

• Kuo HC. Videourodynamic analysis of pathophysiology of men with both storage and voiding lower urinary tract symptoms. Urology. 2007 Aug;70(2):272-6. doi: 10.1016/j.urology.2007.03.063.

  PMID: 17826488 BACKGROUND

• Di Silverio F, Gentile V, De Matteis A, Mariotti G, Giuseppe V, Luigi PA, Sciarra A. Distribution of inflammation, pre-malignant lesions, incidental carcinoma in histologically confirmed benign prostatic hyperplasia: a retrospective analysis. Eur Urol. 2003 Feb;43(2):164-75. doi: 10.1016/s0302-2838(02)00548-1.

  PMID: 12565775 BACKGROUND

• Sciarra A, Mariotti G, Salciccia S, Autran Gomez A, Monti S, Toscano V, Di Silverio F. Prostate growth and inflammation. J Steroid Biochem Mol Biol. 2008 Feb;108(3-5):254-60. doi: 10.1016/j.jsbmb.2007.09.013. Epub 2007 Sep 7.

  PMID: 17935971 BACKGROUND

• Sciarra A, Di Silverio F, Salciccia S, Autran Gomez AM, Gentilucci A, Gentile V. Inflammation and chronic prostatic diseases: evidence for a link? Eur Urol. 2007 Oct;52(4):964-72. doi: 10.1016/j.eururo.2007.06.038. Epub 2007 Jul 2.

  PMID: 17618043 BACKGROUND

• Alcaraz A, Hammerer P, Tubaro A, Schroder FH, Castro R. Is there evidence of a relationship between benign prostatic hyperplasia and prostate cancer? Findings of a literature review. Eur Urol. 2009 Apr;55(4):864-73. doi: 10.1016/j.eururo.2008.11.011. Epub 2008 Nov 21.

  PMID: 19027219 BACKGROUND

• Di Silverio F, Bosman C, Salvatori M, Albanesi L, Proietti Pannunzi L, Ciccariello M, Cardi A, Salvatori G, Sciarra A. Combination therapy with rofecoxib and finasteride in the treatment of men with lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH). Eur Urol. 2005 Jan;47(1):72-8; discussion 78-9. doi: 10.1016/j.eururo.2004.08.024.

  PMID: 15582252 BACKGROUND

• Ozdemir I, Bozkurt O, Demir O, Aslan G, Esen AA. Combination therapy with doxazosin and tenoxicam for the management of lower urinary tract symptoms. Urology. 2009 Aug;74(2):431-5. doi: 10.1016/j.urology.2009.01.088. Epub 2009 Jun 7.

  PMID: 19501883 BACKGROUND

• Jang J, Park EY, Seo SI, Hwang TK, Kim JC. Effects of intravesical instillation of cyclooxygenase-2 inhibitor on the expression of inducible nitric oxide synthase and nerve growth factor in cyclophosphamide-induced overactive bladder. BJU Int. 2006 Aug;98(2):435-9. doi: 10.1111/j.1464-410X.2006.06207.x.

  PMID: 16879691 BACKGROUND

• Falahatkar S, Mokhtari G, Pourreza F, Asgari SA, Kamran AN. Celecoxib for treatment of nocturia caused by benign prostatic hyperplasia: a prospective, randomized, double-blind, placebo-controlled study. Urology. 2008 Oct;72(4):813-6. doi: 10.1016/j.urology.2008.04.069. Epub 2008 Aug 9.

  PMID: 18692876 BACKGROUND

• Djavan B, Waldert M, Zlotta A, Dobronski P, Seitz C, Remzi M, Borkowski A, Schulman C, Marberger M. Safety and morbidity of first and repeat transrectal ultrasound guided prostate needle biopsies: results of a prospective European prostate cancer detection study. J Urol. 2001 Sep;166(3):856-60.

  PMID: 11490233 BACKGROUND

MeSH Terms

Conditions

Prostatic Hyperplasia; Lower Urinary Tract Symptoms

Interventions

Doxazosin; Celecoxib

Condition Hierarchy (Ancestors)

Prostatic Diseases; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Male Urogenital Diseases; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Prazosin; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Dr. Hann-Chorng Kuo
• Organization: Department of Urology, Buddhist Tzu Chi General Hospital and Tzu Chi University

hck@tzuchi.com.tw

886-3-8561825

Study Officials

• Hann-Chorng Kuo, M.D.

  Department of Urology, Buddhist Tzu Chi General Hospital and Tzu Chi University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Department of Urology

Study Record Dates

• First Submitted: August 29, 2012
• First Posted: September 5, 2012
• Study Start: August 1, 2012
• Primary Completion: August 1, 2013
• Study Completion: August 1, 2013
• Last Updated: July 15, 2014
• Results First Posted: June 30, 2014

Record last verified: 2014-07

Locations

TW (1)