Combined Antihypertensive Therapy and Sexual Dysfunction

Hypertension Clinical Trial

Official title:

Effect of Combined Antihypertensive Therapy on Blood Pressure and Sexual Function in Patients With Essential Hypertension

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01238705
• Other study ID #: 0709TCYA068
• Status: Recruiting
• Phase: Phase 4
• First received: October 12, 2010
• Last updated: November 10, 2010
• Start date: April 2008
• Est. completion date: November 2010

Study information

• Verified date: November 2010
• Source: LanZhou University
• Contact: Jing Yu, Professor
• Phone: +86 0931 8942076
• Email: yujing2304[@]126.com
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

This randomized,active controlled study aimed to compare the effects on sexual function of treatment with combined antihypertensive drugs.

The researchers hypothesize that:

1. Both felodipine-irbesartan combination and felodipine-metoprolol combination are effective in lowing blood pressure in patients with essential hypertension.

2. Felodipine-metoprolol combination induces a worse sexual function and a reduction of sex hormone,whereas felodipine-irbesartan combination does not impair sexual function and does not change hormone levels.

3. Oxidative stress decline after both combination regimens. Felodipine-irbesartan combination has a greater impact on oxidative stress indicators than felodipine-metoprolol combination.

Description:

The effects of hypertension and its pharmacotherapy on sexual function are well known in men,although this topic remains unexplored in women.There is evidence suggests that some classes of antihypertensive drugs such as diuretics and beta-blockers have more negative impact on male sexual function than other classes such as calcium channel blockers(CCBs) and angiotensin-converting enzyme inhibitors(ACEI).Some data suggest that angiotensin Ⅱ antagonists（ARBs) not only do not exacerbate sexual function in males,but even improve it.

Treatment with multiple antihypertensive medications was often necessary to attain blood-pressure goals recommended by guidelines.More than two third of patients with 2 or 3 degree of essential hypertension require combination therapy at the beginning of treatment to avoid target organ damage and to minimize the accidence of adverse events.

CCBs were recommended by both JNC-7 and ESH / ESC 2007 hypertension guidelines as the basic for the treatment of hypertension.The purpose of this study is to compare the impacts of different CCB-based antihypertensive drugs combination on sexual behavior in both male and female patients with essential hypertension,thus provide evidences for physicians to increase patients adherence to the treatment regimens beside lowing blood pressure.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 280
• Est. completion date: November 2010
• Est. primary completion date: October 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Patients with essential hypertension.

• Initial hypertension, or without taking any antihypertensive for at least one month.

• Sexual active.

Exclusion Criteria:

• Patients with secondary hypertension.

• Patients with malignant hypertension, coronary heart disease, diabetes, a history of syncope, bradycardia (heart rate <45 beats / min), atrioventricular block(? or ? degree), sick sinus syndrome, congestive heart failure, a history of cerebral vascular accidents, serious hepatic and kidney dysfunction, a history of serious mental illness, pregnant, taking oral exogenous estrogens (including contraceptives), hysterectomy, breastfeeding, a history of alcohol or drug abuse, having serious conflict with sexual partner, severity sexual dysfunction.

• Patients refuse to answer questions, refuse to fill in the questionaires,or do not willing to take blood examination.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypertension
• Sexual Dysfunction

Intervention

Drug:
• Felodipine add Irbesartan
Felodipine Sustained Release Tablets,5mg/day,AstraZeneca Pharmaceutical Co.Ltd., Registration Number: H20030415. Irbesartan,150mg/day, Sanofi - Aventis Pharmaceutical company, Registration Number: H20080074.
• Felodipine add Metoprolol
Felodipine Sustained Release Tablets,5mg/day,AstraZeneca Pharmaceutical Co.Ltd., Registration Number: H20030415. Metoprolol Succinate,47.5mg/day,AstraZeneca Pharmaceutical Co.Ltd., Registration Number: J20050061.

Locations

Country	Name	City	State
China	The Second Hospital of Lanzhou University	Lanzhou	Gansu

Sponsors (1)

Lead Sponsor	Collaborator
LanZhou University

Country where clinical trial is conducted

China, 

References & Publications (27)

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Basson R, Wierman ME, van Lankveld J, Brotto L. Summary of the recommendations on sexual dysfunctions in women. J Sex Med. 2010 Jan;7(1 Pt 2):314-26. doi: 10.1111/j.1743-6109.2009.01617.x. — View Citation

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Fogari R, Preti P, Zoppi A, Corradi L, Pasotti C, Rinaldi A, Mugellini A. Effect of valsartan and atenolol on sexual behavior in hypertensive postmenopausal women. Am J Hypertens. 2004 Jan;17(1):77-81. — View Citation

Fogari R, Zoppi A, Corradi L, Mugellini A, Poletti L, Lusardi P. Sexual function in hypertensive males treated with lisinopril or atenolol: a cross-over study. Am J Hypertens. 1998 Oct;11(10):1244-7. — 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

Jamerson K, Weber MA, Bakris GL, Dahlöf B, Pitt B, Shi V, Hester A, Gupte J, Gatlin M, Velazquez EJ; ACCOMPLISH Trial Investigators. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med. 2008 Dec 4;359(23):2417-28. doi: 10.1056/NEJMoa0806182. — View Citation

Krapf JM, Simon JA. The role of testosterone in the management of hypoactive sexual desire disorder in postmenopausal women. Maturitas. 2009 Jul 20;63(3):213-9. doi: 10.1016/j.maturitas.2009.04.008. Epub 2009 May 31. Review. — View Citation

Lacy F, Kailasam MT, O'Connor DT, Schmid-Schönbein GW, Parmer RJ. Plasma hydrogen peroxide production in human essential hypertension: role of heredity, gender, and ethnicity. Hypertension. 2000 Nov;36(5):878-84. — View Citation

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Meston CM. Validation of the Female Sexual Function Index (FSFI) in women with female orgasmic disorder and in women with hypoactive sexual desire disorder. J Sex Marital Ther. 2003 Jan-Feb;29(1):39-46. — View Citation

Ono H, Minatoguchi S, Watanabe K, Yamada Y, Mizukusa T, Kawasaki H, Takahashi H, Uno T, Tsukamoto T, Hiei K, Fujiwara H. Candesartan decreases carotid intima-media thickness by enhancing nitric oxide and decreasing oxidative stress in patients with hypertension. Hypertens Res. 2008 Feb;31(2):271-9. doi: 10.1291/hypres.31.271. — View Citation

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Vlachopoulos C, Aznaouridis K, Ioakeimidis N, Rokkas K, Tsekoura D, Vasiliadou C, Stefanadi E, Askitis A, Stefanadis C. Arterial function and intima-media thickness in hypertensive patients with erectile dysfunction. J Hypertens. 2008 Sep;26(9):1829-36. doi: 10.1097/HJH.0b013e3283050886. — View Citation

Wassertheil-Smoller S, Blaufox MD, Oberman A, Davis BR, Swencionis C, Knerr MO, Hawkins CM, Langford HG. Effect of antihypertensives on sexual function and quality of life: the TAIM Study. Ann Intern Med. 1991 Apr 15;114(8):613-20. — View Citation

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WRITING GROUP MEMBERS, Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, De Simone G, Ferguson TB, Ford E, Furie K, Gillespie C, Go A, Greenlund K, Haase N, Hailpern S, Ho PM, Howard V, Kissela B, Kittner S, Lackland D, Lisabeth L, Marelli A, McDermott MM, Meigs J, Mozaffarian D, Mussolino M, Nichol G, Roger VL, Rosamond W, Sacco R, Sorlie P, Roger VL, Thom T, Wasserthiel-Smoller S, Wong ND, Wylie-Rosett J; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2010 update: a report from the American Heart Association. Circulation. 2010 Feb 23;121(7):e46-e215. doi: 10.1161/CIRCULATIONAHA.109.192667. Epub 2009 Dec 17. Erratum in: Circulation. 2010 Mar 30;121(12):e260. Stafford, Randall [corrected to Roger, Véronique L]. Circulation. 2011 Oct 18;124(16):e425. — View Citation

* Note: There are 27 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Female Sexual Function Index (FSFI)	The Female Sexual Function Index (FSFI) is a multidimensional self-report scale for assessing sexual function in women.The FSFI hase been validated in women with various sexual disorders,and in non-dysfunctional controls showing good discriminant validity,internal consistency,and test-retest reliability.	48 weeks	Yes
Primary	International Index of Erectile Function(IIEF)	The 15-item International Index of Erectile Function (IIEF) was developed to diagnose the presence and severity of erectile dysfunction (ED).	48 weeks	Yes
Secondary	Change of Systolic Blood Pressure in 2 Weeks	The decrease of systolic blood pressure compared with baseline. Baseline is blood pressure in 0 week.; BP is measured using a calibrated standard mercury sphygmomanometer.After the patient has been seated for 15 minutes,sitting BP is measured 2 times at 1- to 2-minutes intervals,The mean of 2 sitting BP measurements is used as the sitting BP value for that visit;If the difference between the 2 measurements is over 5mmHg,BP should be measured again, and the average of 3 measurements will be taken.	2 weeks	No
Secondary	Change of Systolic Blood Pressure in 4 Weeks	The decrease of systolic blood pressure compared with baseline. Baseline is blood pressure in 0 week.	4 weeks	No
Secondary	Change of Systolic Blood Pressure in 8 Weeks	The decrease of systolic blood pressure compared with baseline. Baseline is blood pressure in 0 week.	8 weeks	No
Secondary	Change of Systolic Blood Pressure in 12 Weeks	The decrease of systolic blood pressure compared with baseline. Baseline is blood pressure in 0 week	12 weeks	No
Secondary	Change of Systolic Blood Pressure in 24 Weeks	The decrease of systolic blood pressure compared with baseline. Baseline is blood pressure in 0 week.	24 weeks	No
Secondary	Change of Systolic Blood Pressure in 48 Weeks	The decrease of systolic blood pressure compared with baseline. Baseline is blood pressure in 0 week	48 weeks	No
Secondary	Change of Diastolic Blood Pressure in 2 Weeks	The decrease of diastolic blood pressure compared with baseline. Baseline is blood pressure in 0 week	2 weeks	No
Secondary	Change of Diastolic Blood Pressure in 4 Weeks	The decrease of diastolic blood pressure compared with baseline. Baseline is blood pressure in 0 week	4 weeks	No
Secondary	Change of Diastolic Blood Pressure in 8 Weeks	The decrease of diastolic blood pressure compared with baseline. Baseline is blood pressure in 0 week	8 weeks	No
Secondary	Change of Diastolic Blood Pressure in 12 Weeks	The decrease of diastolic blood pressure compared with baseline. Baseline is blood pressure in 0 week.	12 weeks	No
Secondary	Change of Diastolic Blood Pressure in 24 Weeks	The decrease of diastolic blood pressure compared with baseline. Baseline is blood pressure in 0 week.	24 weeks	No
Secondary	Change of Diastolic Blood Pressure in 48 Weeks	The decrease of diastolic blood pressure compared with baseline. Baseline is blood pressure in 0 week.	48 weeks	No
Secondary	Serum Estradiol in 24 Weeks	Fasting blood samples are taken at 8:00-10:00.After quiescence for 1h and centrifuged (3500rpm/min * 15min), serum samples are extracted and preserved in -80 ?. Use hemiluminescent radioimmunoassay to detect the level of estradiol in serum sample.	24 weeks	No
Secondary	Serum Estradiol in 48 Weeks		48 weeks	No
Secondary	Serum Testosterone in 24 Weeks	Fasting blood samples are taken at 8:00-10:00.After quiescence for 1h and centrifuged (3500rpm/min * 15min), serum samples are extracted and preserved in -80 ?. Use hemiluminescent radioimmunoassay to detect the level of testosterone in serum sample.	24 weeks	No
Secondary	Serum Testosterone in 48 Weeks		48 weeks	No
Secondary	Serum MDA in 24 Weeks	Among many oxidative stress biological indicators,malondialdehyde (MDA),the secondary products of lipid peroxidation,is the most representative and most studied polyunsaturated fatty acid peroxidation.; Fasting blood samples are taken at 8:00-10:00.After quiescence for 1h and centrifuged (3500rpm/min * 15min), serum samples are extracted and preserved in -80 ?. Use ELISA to detect the level of MDA in serum samples.	24 weeks	No
Secondary	Serum MDA in 48 Weeks		48 weeks	No
Secondary	Serum 8-OHdG in 24 Weeks	Reactive oxygen species (ROS) produced either endogenously or exogenously can attack lipid, protein and nucleic acid simultaneously in the living cells. In nuclear and mitochondrial DNA, 8-hydroxydeoxyguanosine (8-OHdG) is produced during DNA repair and its measurement be useful as a marker of DNA lesion.; Fasting blood samples are taken at 8:00-10:00.After quiescence for 1h and centrifuged (3500rpm/min * 15min), serum samples are extracted and preserved in -80 ?. Use ELISA to detect the level of 8-OHdG in serum samples.	24 weeks	No
Secondary	Serum 8-OHdG in 48 Weeks		48 weeks	No
Secondary	Serum HNE in 24 Weeks	4 - hydroxy-nonyl acid (HNE) is a strong toxicity end product of lipid peroxidation.; Fasting blood samples are taken at 8:00-10:00.After quiescence for 1h and centrifuged (3500rpm/min * 15min), serum samples are extracted and preserved in -80 ?. Use ELISA to detect the level of HNE in serum samples.	24 weeks	No
Secondary	Serum HNE in 48 Weeks		48 weeks	No