Improvement of Erectile Dysfunction by Fluvastatin in Patients With Cardiovascular Risk Factors

Impotence Clinical Trial

Official title:

Influence of Treatment With the HMG-CoA-Reductase Inhibitor Fluvastatin on Erectile Function in Patients With Cardiovascular Risk-Factors and Erectile Dysfunction

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00382161
• Other study ID #: 48/05
• Secondary ID: EudraCT-No.:2006
• Status: Withdrawn
• Phase: Phase 3
• First received: September 27, 2006
• Last updated: February 12, 2009
• Start date: October 2006
• Est. completion date: December 2007

Study information

• Verified date: February 2009
• Source: University Hospital, Saarland
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to determine the effect of fluvastatin on penile arterial blood flow and erectile function in patients with arteriogenic ED and cardiovascular risk factors.

Description:

Physiology of erection is mainly dependent on endothelial NO-production with consecutive activation of guanylate-cyclase. Pleiotropic effects of statins are well known regarding the increase of endothelial function. Thus, activation of endothelial NO-synthase could raise the activation of guanylate-cyclase with a consecutive relaxation of smooth muscle cells in the penile arteries and the corpus cavernosum leading to an improvement of erectile function. Therefore, statins are supposed to be effective in the treatment of erectile dysfunction, especially in patients with cardiovascular risk-factors with underlying endothelial dysfunction.

The effect of fluvastatin on penile blood-flow and erectile function in patients with arteriogenic erectile dysfunction and cardiovascular risk factors will be determined in a cross-over design. Patients were either treated with fluvastatin-sodium 80mg or placebo for 8 weeks. After a wash-out of 4 weeks, treatment will be switched (placebo / fluvastatin-sodium). Penile blood flow measurement and assessment of erectile function with the IIEF-5-score and the KEED-score will be performed at baseline, after 8 weeks of treatment, after 4 weeks wash-out and after cross-over treatment (8 weeks).

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 20
• Est. completion date: December 2007
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• male

• age > 18 years

• arteriogenic erectile dysfunction (penile blood flow - peak systolic velocity<30cm/s, diastolic velocity<5cm/s)

• two or more cardiovascular risk factors (smoking, hypertension, hyperlipoproteinaemia, family history of atherosclerosis, oral treated diabetes mellitus with a HbA1c<7%)

• stable course of disease without expected changes in medical treatment during the next 3 months

• written informed consent

• no statin-treatment so far

Exclusion Criteria:

• known hypersensitivity or anaphylaxis against a statin

• active liver disease or unclear increase of transaminases, cholestasis or myopathy

• acute cardiovascular event (myocardial infarction, stroke, PTCA, vascular surgery) within 3 months before randomization

• clinical signs of heart failure or reduced left ventricular function

• current treatment with lipid lowering drugs

• insulin dependent diabetes mellitus or orally treated diabetes mellitus with a HbA1c-value >6.9%

• erectile dysfunction due to hormone disorders

• known malignant tumor

• known disposition to priapism

• patients with morphological changes of the penis (i.e. deviation) or penis-prosthesis

• current treatment with anticoagulants

• current treatment with immunosuppressive drugs, phenytoin, erythromycin, gemfibrozil or nicotinic acid derivates

• absence or inability of written informed consent

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Erectile Dysfunction
• Impotence

Intervention

Drug:
• Fluvastatin-sodium

Locations

Country	Name	City	State
Germany	University Hospital of the Saarland	Homburg	Saarland

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Saarland	Novartis

Country where clinical trial is conducted

Germany, 

References & Publications (15)

Aversa A, Isidori AM, Spera G, Lenzi A, Fabbri A. Androgens improve cavernous vasodilation and response to sildenafil in patients with erectile dysfunction. Clin Endocrinol (Oxf). 2003 May;58(5):632-8. — View Citation

Braun M, Wassmer G, Klotz T, Reifenrath B, Mathers M, Engelmann U. Epidemiology of erectile dysfunction: results of the 'Cologne Male Survey'. Int J Impot Res. 2000 Dec;12(6):305-11. — View Citation

Büyükafsar K, Un I. Effects of the Rho-kinase inhibitors, Y-27632 and fasudil, on the corpus cavernosum from diabetic mice. Eur J Pharmacol. 2003 Jul 11;472(3):235-8. — View Citation

Chitaley K, Wingard CJ, Clinton Webb R, Branam H, Stopper VS, Lewis RW, Mills TM. Antagonism of Rho-kinase stimulates rat penile erection via a nitric oxide-independent pathway. Nat Med. 2001 Jan;7(1):119-22. — View Citation

Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ, McKinlay JB. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol. 1994 Jan;151(1):54-61. — View Citation

Grimm RH Jr, Grandits GA, Prineas RJ, McDonald RH, Lewis CE, Flack JM, Yunis C, Svendsen K, Liebson PR, Elmer PJ. Long-term effects on sexual function of five antihypertensive drugs and nutritional hygienic treatment in hypertensive men and women. Treatment of Mild Hypertension Study (TOMHS). Hypertension. 1997 Jan;29(1 Pt 1):8-14. — View Citation

Impotence. NIH Consens Statement. 1992 Dec 7-9;10(4):1-33. Review. — View Citation

Kinsey AC, Pomeroy W, Martin CE. Sexual behavior in the human man. 1948:218-262

Laufs U, Wassmann S, Hilgers S, Ribaudo N, Böhm M, Nickenig G. Rapid effects on vascular function after initiation and withdrawal of atorvastatin in healthy, normocholesterolemic men. Am J Cardiol. 2001 Dec 1;88(11):1306-7. — View Citation

Nangle MR, Cotter MA, Cameron NE. Effects of rosuvastatin on nitric oxide-dependent function in aorta and corpus cavernosum of diabetic mice: relationship to cholesterol biosynthesis pathway inhibition and lipid lowering. Diabetes. 2003 Sep;52(9):2396-402. — View Citation

Rosen RC, Cappelleri JC, Smith MD, Lipsky J, Peña BM. Development and evaluation of an abridged, 5-item version of the International Index of Erectile Function (IIEF-5) as a diagnostic tool for erectile dysfunction. Int J Impot Res. 1999 Dec;11(6):319-26. — View Citation

Speel TG, van Langen H, Wijkstra H, Meuleman EJ. Penile duplex pharmaco-ultrasonography revisited: revalidation of the parameters of the cavernous arterial response. J Urol. 2003 Jan;169(1):216-20. — View Citation

Virag R, Bouilly P, Frydman D. Is impotence an arterial disorder? A study of arterial risk factors in 440 impotent men. Lancet. 1985 Jan 26;1(8422):181-4. — View Citation

Wassmann S, Ribaudo N, Faul A, Laufs U, Böhm M, Nickenig G. Effect of atorvastatin 80 mg on endothelial cell function (forearm blood flow) in patients with pretreatment serum low-density lipoprotein cholesterol levels <130 mg/dl. Am J Cardiol. 2004 Jan 1;93(1):84-8. — View Citation

Wei M, Macera CA, Davis DR, Hornung CA, Nankin HR, Blair SN. Total cholesterol and high density lipoprotein cholesterol as important predictors of erectile dysfunction. Am J Epidemiol. 1994 Nov 15;140(10):930-7. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Penile blood flow (peak systolic velocity, resistance index, pulsatility index) after 8 weeks of treatment.
Secondary	Erectile function assessed with the IIEF-5 score (international index of erectile function) after 8 weeks of treatment.
Secondary	Erectile function assessed with the KEED score (cologne questionnaire of erectile function) after 8 weeks of treatment.