Effect of Pentoxifylline and Zinc Co-administration in Patients With Oligoasthenoteratozoospermia (OAT)

Evaluating the Therapeutic Effect of Pentoxifylline and Zinc Co-administration in Patients With Idiopathic Oligoasthenoteratozoospermia

The aim of this study is to investigate the impact of co-administration of Pentoxifylline and Zinc sulfate on oxidative stress, apoptosis, and inflammation, sperm capacitation and parameters in infertile men.

Study Overview

• Status: Not yet recruiting
• Conditions: Idiopathic Infertility
• Intervention / Treatment: Drug: Placebo; Drug: Pentoxifylline; Drug: zinc; Drug: zinc + pentoxifylline

Detailed Description

This study will be performed as a double-blind randomized clinical trial on idiopathic infertile men (including oligoasthenosospermia, dyspnea, astheno-teratozoospermia, oligo-astheno-teratozoospermia) referred to Shafa Infertility Clinic. Patient satisfaction, non-use of contraceptives, men aged 25 to 43 years and idiopathic infertility according to WHO criteria (World Health, 2010) are our study criteria. A food questionnaire is also taken from them to identify patients. Any medication that may affect sperm production should be discontinued within three months of the study.

Sampling and administration of pentoxifylline and zinc:

Preparation and analysis of semen samples are performed according to WHO 2010 recommendations. Semen samples are prepared by masturbating after a 3 to 5 day abstinence period. Two semen samples from these men, one before and the other after the intervention, are evaluated for basic parameters. For liquefaction, semen samples are incubated for 30 to 60 minutes at 37 ° C. Microscopic tests are performed to evaluate indicators such as sperm concentration in semen, motility and sperm morphology. Objectives and study methods are explained to patients who meet the inclusion criteria. Written consent is then obtained from the candidate. Body mass index (BMI) is assessed for patients. Also, at the beginning of the study, 5 cc of blood is taken from patients to measure reproductive hormones.

• Study Type: Interventional
• Enrollment (Anticipated): 140
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Idiopathic infertile men
• have had at least one year of unprotected intercourse infertility
• Sperm parameters abnormality

Exclusion Criteria:

• Men with varicocele
• Hypersensitivity to pentoxifylline & zinc,
• pelvic organic pathologies
• congenital adrenal hyperplasia
• thyroid dysfunction
• Cushing's syndrome
• hyper prolactinemia
• androgen secreting neoplasia
• diabetes mellitus
• consumption of medications affecting carbohydrate metabolism
• severe hepatic
• pancreatitis
• kidney diseases
• gallbladder diseases
• Patients with alcohol consumption
• Patients who use cigarettes and drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: placebo group; Control group: oral rehydration salts (ORS, Poursina, Tehran, Iran), two times daily	Drug: Placebo; Infertile men referred to the infertility treatment center who, have had at least one year of unprotected intercourse, Natural fertility has not happened in their spouse. These men will all be married These men will be between the ages of 20 and 50. According to WHO criteria, Sperm parameters abnormalities should be observed in at least two spermogram within 2 weeks. Candidates receive two placebo tablets daily; Other Names: hydration solution
EXPERIMENTAL: pentoxifylline group; Intervention group 1: received pentoxifylline (TRENTAL 400 mg modified release tablets, OSPS; 400 mg ,two times daily)	Drug: Pentoxifylline; Infertile men referred to the infertility treatment center who, have had at least one year of unprotected intercourse, Natural fertility has not happened in their spouse. These men will all be married These men will be between the ages of 20 and 50. According to WHO criteria, Sperm parameters abnormalities should be observed in at least two spermogram within 2 weeks. Candidates receive two trental tablets daily; Other Names: Trental
EXPERIMENTAL: Zinc group; Intervention group 2: received zinc ( Zinc Sulfate 220mg Capsules,One time daily)	Drug: zinc; Infertile men referred to the infertility treatment center who, have had at least one year of unprotected intercourse, Natural fertility has not happened in their spouse. These men will all be married These men will be between the ages of 20 and 50. According to WHO criteria, Sperm parameters abnormalities should be observed in at least two spermogram within 2 weeks. Candidates receive one zinc sulfate tablet daily; Other Names: zinc sulfate
EXPERIMENTAL: pentoxifylline+ zinc group; Intervention group 3: received pentoxifylline+ zinc (TRENTAL 400 mg modified release tablets, OSPS; 400 mg ,two times daily + Zinc Sulfate 220mg Capsules,One time daily )	Drug: zinc + pentoxifylline; Infertile men referred to the infertility treatment center who, have had at least one year of unprotected intercourse, Natural fertility has not happened in their spouse. These men will all be married These men will be between the ages of 20 and 50. According to WHO criteria, Sperm parameters abnormalities should be observed in at least two spermogram within 2 weeks. Candidates receive two pentoxifylline tablets+ one zinc tablet daily; Other Names: zinc sulfate+ trental

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
count of sperm	count of sperm(In per million - with the help of a neobar slide and microscopic observation	One week after starting the medication
motility of sperm	motility of sperm: Calculate the percentage of motile sperm using microscopic observation	One week after starting the medication
morphology of sperm	Calculate the percentage of sperm with a normal shape with the help of Papanic staining	One week after starting the medication
Malon di aldehyd evaluate	Malondialdehyde (nmol/mL), will be measured using related experimental kits	One week after starting the medication
ROS evaluate	reactive oxygen species (ROS (RLU/s)), will be measured using related experimental kits	One week after starting the medication
TAC (Total Antioxidant Capacity) evaluate	total antioxidant capacity (TAC (/m / l)) will be measured using related experimental kits	One week after starting the medication
FSH hormon	FSH (IU / L) will be measured from the blood serum of volunteers using ELISA kit	One week after starting the medication
LH hormon	LH (IU / L) will be measured from the blood serum of volunteers using ELISA kit	One week after starting the medication
Testosteron hormon	testosterone (nanomolar per liter) will be measured from the blood serum of volunteers using ELISA kit	One week after starting the medication
TNF α( Tissue necrosis Factor)	TNF α( Tissue necrosis Factor) (pg/mL) as an inflammatory factor will be measured using related experimental kit	One week after starting the medication
Interleukin-6 (IL-6)	Interleukin-6 (IL-6)/(pg/mL) as an inflammatory factor will be measured using related experimental kit	One week after starting the medication
Sperm DNA Fragmentation Assay(SDFA)	DNA fragmentation will be assessed using an SDFA kit and microscopic observations (as a percentage of damaged sperm).	One week after starting the medication

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
caspase 3 expression	expression of caspase 3 gen (in p.c) using real-time PCR and Western blot	3 months
BAX expression	expression of BAX gen(in p.c) using real-time PCR and Western blot	3 months
BCL 2 expression	expression of BCL 2 gen (in p.c) using real-time PCR and Western blot	3 months

Collaborators and Investigators

• Sponsor: Arak University of Medical Sciences

Publications and helpful links

General Publications

• Dadgar Z, Shariatzadeh SMA, Mehranjani MS, Kheirolahi A. The therapeutic effect of co-administration of pentoxifylline and zinc in men with idiopathic infertility. Ir J Med Sci. 2023 Feb;192(1):431-439. doi: 10.1007/s11845-022-02931-0. Epub 2022 Feb 19.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): January 1, 2022
• Primary Completion (ANTICIPATED): January 10, 2022
• Study Completion (ANTICIPATED): May 28, 2022

Study Registration Dates

• First Submitted: November 5, 2021
• First Submitted That Met QC Criteria: December 1, 2021
• First Posted (ACTUAL): December 14, 2021

Study Record Updates

• Last Update Posted (ACTUAL): January 3, 2022
• Last Update Submitted That Met QC Criteria: December 13, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infertility, Male; Infertility; Oligospermia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protective Agents; Dermatologic Agents; Trace Elements; Micronutrients; Antioxidants; Phosphodiesterase Inhibitors; Free Radical Scavengers; Radiation-Protective Agents; Astringents; Zinc; Zinc Sulfate; Pentoxifylline
• Other Study ID Numbers: 96/197

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No