Protocol summary

Summary
Methadone and Buprenorphine have been used as opioid Substitution Treatment (OST) in the world since 40 & 18 years ago in order. Regardless of short period experience in the past, these treatments have 14 & 10 years history in Iran respectively. There is a lot of questions about unwanted side effects of these medications on structure & function of different organs of body which concerns clients & worries therapists. One of organs with most sensitivity about that, is Genital system and common questions of mostly young clients on maintenance treatments, especially those who tend to have child in the future, is about probable effects of methadone & buprenorphine on sperm & fertility. Accurate & scientific answer to this question and select of appropriate medication for each client, diminishes their concerns and increases therapeutic alliance. According to high prevalence & morbidity of opioid use disorder especially in young & middle-aged men, and widespread providing of OST with methadone & buprenorphine, we decided to substitute methadone by buprenorphine in men who receive OST and survey the effect of this shift on sexual hormones & sperm analysis. The study will be done on 40 participants from Rouyan institute who their infertility has been established and in the routine diagnostic procedures, there was not any finding except methadone consumption as an opioid substitution treatment. Primary routine laboratory tests (including TT, FT, LH, FSH, SHBG, PL, Semen Analysis) will done in the Rouyan Institute and after filling of inclusion criteria, clients will be refer to an experienced clinic in prescription of buprenorphine with appropriate access for continuing of study. Inclusion criteria: 1) men between 18 to 50 y/o; 2) at least 6 months on Opioid Substitution Treatment & 3 months from last illegal opioid use; 3) daily Methadone dose less than 60 mg/d; 4) certification of therapist physician on stability & readiness of client for shifting from methadone to buprenorphine; 5) diagnosis of methadone as the most important factor for undesirable hormonal & seminal analysis; 6) written & signed informed consent form. The participants will stay on 2 groups randomly. In the study group methadone will be substituted with buprenorphine and in the control group methadone will be continued. In both groups laboratory test including sex hormones (TT, FT, LH, FSH, SHBG, PL) and semen analysis will be done 3 times: before intervention,3 months & 6 months after beginning of intervention. Exclusion criteria: 1) evidence or signs of laps & relapse in buprenorphine treatment even with appropriate dose; 2) absence from treatment more than 2 consecutive or 3 undulant weeks; 3) absence from screening opioid urine test more than 2 consecutive or 3 undulant sessions; 4) absence from hormonal & seminal analysis more than 2 weeks after appointed time; 5) intolerance of methadone dose reduction for shifting to buprenorphine; 6) intolerance of buprenorphine side effects.

General information

Acronym
IRCT registration information
IRCT registration number: IRCT2016011626040N1
Registration date: 2016-04-26, 1395/02/07
Registration timing: registered_while_recruiting

Last update:
Update count: 0
Registration date
2016-04-26, 1395/02/07
Registrant information
Name
Maryam Farahmandfar
Name of organization / entity
Tehran University of Medical Sciences
Country
Iran (Islamic Republic of)
Phone
+98 21 8899 1118
Email address
mfarahmandfar@sina.tums.ac.ir
Recruitment status
Recruitment complete
Funding source
Tehran University of Medical Sciences
Expected recruitment start date
2016-04-03, 1395/01/15
Expected recruitment end date
2017-04-04, 1396/01/15
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Survey on Effect of Methadone to Buprenorphine Shift in the Maintenance Treatment on Profile of Gonadal Hormones and Semen Analysis of Infertile Men
Public title
Effect of Substitution of Methadone by Buprenorphine on Gonadal Hormones and Semen
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria: men between 18 to 50 y/o; at least 6 months on Opioid Substitution Treatment & 3 months from last illegal opioid use; daily Methadone dose less than 60 mg/d; certification of therapist physician on stability & readiness of client for shifting from methadone to buprenorphine; diagnosis of methadone as the most important factor for undesirable hormonal & seminal analysis; written & signed informed consent form. Exclusion criteria: evidence or signs of laps & relapse in buprenorphine treatment even with appropriate dose; absence from treatment more than 2 consecutive or 3 undulant weeks; absence from screening opioid urine test more than 2 consecutive or 3 undulant sessions; absence from hormonal & seminal analysis more than 2 weeks after appointed time; intolerance of methadone dose reduction for shifting to buprenorphine; intolerance of buprenorphine side effects.
Age
From 18 years old to 50 years old
Gender
Male
Phase
N/A
Groups that have been masked
No information
Sample size
Target sample size: 40
Randomization (investigator's opinion)
Randomized
Randomization description
Blinding (investigator's opinion)
Not blinded
Blinding description
Placebo
Not used
Assignment
Parallel
Other design features

Secondary Ids

empty

Ethics committees

1

Ethics committee
Name of ethics committee
Tehran University of Medical Sciences
Street address
Secretariat of Ethics Committee, Sixth Floor, Tehran University of Medical Sciences, Qhods St. Keshavarz Blvd.
City
Tehran
Postal code
Approval date
2015-11-16, 1394/08/25
Ethics committee reference number
IR.TUMS.REC.1394.1172

Health conditions studied

1

Description of health condition studied
Male infertility in opioid substitution treatment
ICD-10 code
N46
ICD-10 code description
Male infertility

Primary outcomes

1

Description
Follicle-stimulating hormone (FSH) blood level
Timepoint
Before intervention, 3 months after beginning of intervention, 6 months after beginning of intervention
Method of measurement
mIU/ml (ELISA)

2

Description
Luteinizing hormone (LH) blood level
Timepoint
Before intervention, 3 months after beginning of intervention, 6 months after beginning of intervention
Method of measurement
IU/L (ELISA)

3

Description
Free Testosterone (FT) blood level
Timepoint
Before intervention, 3 months after beginning of intervention, 6 months after beginning of intervention
Method of measurement
pg/ml (ELISA)

4

Description
Total Testosterone (TT) blood level
Timepoint
Before intervention, 3 months after beginning of intervention, 6 months after beginning of intervention
Method of measurement
ng/ml (ELISA)

5

Description
Prolactin (PRL) blood level
Timepoint
Before intervention, 3 months after beginning of intervention, 6 months after beginning of intervention
Method of measurement
ng/ml (ELISA)

6

Description
Sex Hormone Binding Globulin (SHBG) blood level
Timepoint
Before intervention, 3 months after beginning of intervention, 6 months after beginning of intervention
Method of measurement
nmol/l (ELISA)

7

Description
Semen Volume
Timepoint
Before intervention, 3 months after beginning of intervention, 6 months after beginning of intervention
Method of measurement
Ml

8

Description
Level of PH of semen
Timepoint
Before intervention, 3 months after beginning of intervention, 6 months after beginning of intervention
Method of measurement
Ph Scale

9

Description
Number of spermatozoid in 1 Ml of semen
Timepoint
Before intervention, 3 months after beginning of intervention, 6 months after beginning of intervention
Method of measurement
Million/ml

10

Description
Time for fluidity of semen
Timepoint
Before intervention, 3 months after beginning of intervention, 6 months after beginning of intervention
Method of measurement
minute

11

Description
Shape of spermatozoides
Timepoint
Before intervention, 3 months after beginning of intervention, 6 months after beginning of intervention
Method of measurement
Percentage of spermatozoides with normal shape

12

Description
Normal motility of spermatozoides
Timepoint
Before intervention, 3 months after beginning of intervention, 6 months after beginning of intervention
Method of measurement
Percentage of spermatozoides with normal forward motion

Secondary outcomes

1

Description
Daily methadone dose
Timepoint
Before substitution by buprenorphine
Method of measurement
mg/d

2

Description
Daily buprenorphine dose
Timepoint
After substitution of methadone
Method of measurement
mg/d

Intervention groups

1

Description
According to a randomized categorization, participants will be classified in 2 groups that will be informed. In the intervention group methadone will be substitute with buprenorphine, and maintenance treatment will continue for 6 months. Prescribed medication in the study group is buprenorphine hydrochloride (2 mg SL tablet) manufactured by Faranchimie, 8-16 mg/day, single dose for 6 months. Sampling for laboratory tests (5 cc blood for sex hormones and Seminal fluid volume in 1 ejaculation for semen analysis) will be taken 3 times: before intervention, 3 months, & 6 months after beginning of intervention. Opioid screening test will be done (by taking urine sample 10 cc) every month.
Category
Treatment - Drugs

2

Description
In the control group methadone will be continued as maintenance treatment for 6 months. prescribed medication in the control group is 5 mg methadone hydrochloride tablet, 40-60 mg/day, single dose, for 6 months. Sampling for laboratory tests (5 cc blood for sex hormones and Seminal fluid volume in 1 ejaculation for semen analysis) will be taken 3 times: before intervention, 3 months, & 6 months after beginning of intervention. Opioid screening test will be done (by taking urine sample 10 cc) every month.
Category
Treatment - Drugs

Recruitment centers

1

Recruitment center
Name of recruitment center
Iranian National Center for Addiction Studies
Full name of responsible person
Mohammad Reza Haddadi
Street address
No. 669, Qazvin Square, Sout Kargar Avenue
City
Tehran

Sponsors / Funding sources

1

Sponsor
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Nasim Vosoughi, Ph.D
Street address
No. 88, School of Advanced Technologies in Medicine, Italia st. , Keshavarz Blvd.
City
Tehran
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Tehran University of Medical Sciences
Proportion provided by this source
100
Public or private sector
empty
Domestic or foreign origin
empty
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
empty

Person responsible for general inquiries

Contact
Name of organization / entity
Iranian National Center for Addiction Studies
Full name of responsible person
Mohammad Reza Haddadi
Position
Medical Degree/ Director of Buprenorphine Clinic
Other areas of specialty/work
Street address
No. 669, Qazvin Square, South Kargar Avenue
City
Tehran
Postal code
1336616357
Phone
+98 21 5542 3728
Fax
+98 21 5547 2232
Email
incas@tums.ac.ir
Web page address
http:/incas.tums.ac.ir

Person responsible for scientific inquiries

Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Maryam Farahmandfar
Position
Ph.D in Physiology
Other areas of specialty/work
Street address
No.88, Italia Ave., Qods St., Keshavarz Blvd., School of Advanced Technologies in Medicine
City
Tehran
Postal code
1417755469
Phone
+98 21 4305 2000
Fax
+98 21 8899 1117
Email
education-satim @tums.ac.ir
Web page address
http://satim.tums.ac.ir/

Person responsible for updating data

Contact
Name of organization / entity
Iranian National Center for Addiction Studies
Full name of responsible person
Mohammd Reza Haddadi
Position
Medical Degree/ Director of Buprenorphine clinic
Other areas of specialty/work
Street address
No.669, Qazvin square, South Kargar Avenue
City
Tehran
Postal code
1336616357
Phone
+98 21 5542 3728
Fax
+98 21 5541 2232
Email
incas@tums.ac.ir
Web page address
http://incas.tums.ac.ir/

Sharing plan

Deidentified Individual Participant Data Set (IPD)
empty
Study Protocol
empty
Statistical Analysis Plan
empty
Informed Consent Form
empty
Clinical Study Report
empty
Analytic Code
empty
Data Dictionary
empty
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