Bupropion in Sexual Dysfunction Among Methadone Maintenance Treatment Men

• Sponsor: University of Malaya (Other)
• Overall Status: Completed
• CT.gov ID: NCT02593396
• Collaborator: (none)
• Enrollment: 80
• Location: 1
• Arms: 2
• Actual Duration (Months): 24
• Patients Per Site Per Month: 3.3

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the tolerability, safety, and efficacy of bupropion hydrochloride sustained-release in the treatment of sexual dysfunction in men on methadone maintenance therapy.

Condition or Disease	Intervention/Treatment	Phase
Sexual Dysfunctions, Psychological; Hypoactive Sexual Desire Disorder; Erectile Dysfunctions	Drug: Bupropion hydrochloride sustained-release; Drug: placebo	Phase 2

Detailed Description

This is a single-center (University Malaya Medical Centre), randomized, double-Blind, placebo-controlled versus bupropion hydrochloride sustained-releases study trial on 70 men who have methadone emergent sexual dysfunction. Bupropion hydrochloride sustained-release (Wellbutrin SR) 150mg once a day for 7 days then 150mg twice a day for 42 days. Taken orally by the subjects.The total duration of the study is expected to be 24 months. 20months for subject recruitment and 4 months for final subject follow-up.

The primary endpoint is Mean improvement in scores on the Clinical Global Impression Scale adapted for sexual Function (CGI-SF). Secondary endpoints are Change from baseline International Index of Erectile Function (IIEF-15) score. Mean improvement in scores on the sexual desire inventory 2 (SDI2). Other evaluation included: Montgomery-Åsberg Depression Rating Scale (MADRS- Malay version ), Mini International Neuropsychiatric Interview (M.I.N.I), Opiate Treatment Index (OTI), World health organization Quality of Life-Brief Scale (WHOQoL-Brief, Malay version), Malay Version of the Golombok-Rust Inventory of Marital State (Mal-GRIMS) and Rapid urine drug test. Safety evaluation included: Incidence of adverse events. Data will be analyzed using linear mixed-effects model.

Study Design

• Study Type: Interventional
• Actual Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Trial Of Bupropion Hydrochloride Sustained-Release In The Treatment Of Sexual Dysfunction In Men On Methadone Maintenance Therapy
• Actual Study Start Date: Dec 1, 2015
• Actual Primary Completion Date: Dec 1, 2017
• Actual Study Completion Date: Dec 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: placebo Placebo BD	Drug: placebo; Up to 70 eligible patients will be randomly assigned to Bupropion Hydrochloride Sustained-Release or placebo treatment groups in a 1:1 ratio using a computer-generated table of random numbers through the use of the Randomization.com program. Subjects will be randomized to to Bupropion Hydrochloride Sustained-Release 150mg b.d. (n = 35) or placebo b.d (n = 35)
Experimental: Active Bupropion hydrochloride sustained-release 150mg BD	Drug: Bupropion hydrochloride sustained-release; Up to 70 eligible patients will be randomly assigned to Bupropion Hydrochloride Sustained-Release or placebo treatment groups in a 1:1 ratio using a computer-generated table of random numbers through the use of the Randomization.com program. Subjects will be randomized to to Bupropion Hydrochloride Sustained-Release 150mg b.d. (n = 35) or placebo b.d (n = 35)The study drug will be repacked in the standard capsules by the research assistant who is not involved in the assessment of the study. The study drug and placebo will be packaged in sets of 11 (1 tablet per day for 3 days, followed by 2 tablets per day for 4 days.) for the first week. Subsequently, the study drug and placebo will be packaged in sets of 14 (2 tablets per day for 7 days.).; Other Names: wellbutrin SR

Outcome Measures

Primary Outcome Measures

1. Number of Participants With a Score of ≤2 (Much/Very Much Improved) on the Clinical Global Impression Scale Adapted for Sexual Function (CGI-SF) at Week 6 Between Placebo and Active Group [assessed at baseline, day 14(week 2), day 28(week four) and day 42 (week 6), data at day 42 (week 6) reported]

   This scale assesses the changes of the sexual function. Scores range from 1 (normal/very much improved) to 7 (most extreme sexual dysfunction/very much worse). Lower scores indicate better sexual functioning.

Secondary Outcome Measures

1. Mean Difference of Malay Version of International Index of Erectile Function (Mal-IIEF-15) at Week 6 Between Placebo and Active Group [assessed at baseline, day 14(week 2), day 28(week four) and day 42 (week 6), data at day 42 (week 6) reported]

   Mal-IIEF-15 is a 15-item, multi-dimensional self-reporting instrument for the evaluation of male sexual function for the past 4 weeks, consisted of five domains; 1) Erectile Function: sum of items 1, 2, 3, 4, 5 & 15. Total score range =1-30. 2) Orgasmic Function: sum of items 9 and 10. Total score range = 0 -10. 3) Sexual Desire: sum of items 11 and 12. Total score range = 2 -10. 4) Intercourse Satisfaction : sum of scores for Questions 6, 7 and 8. Total score range = 0 -15. 5) Overall Satisfaction: sum of items 13 and 14.Total score range = 2 -10. Items 1-10 is 6-point Likert-type scale from '0' (= No sexual activity) to '5' (= Almost always or always). Items 11-15 is 5-point Likert-type scale from '1' (= Almost never or never) to '5 '(= 'Almost always or always').The total Mal-IIEF-15 range from 5 (minimum) to 75 (Maximum). Higher score indicates better outcome in all domain.

2. Mean Difference of Malay Version of Sexual Desire Inventory 2 (SDI-2) Score at Weeks 6 Between Placebo and Active Groups [Assessed at baseline, day 14(week 2), day 28(week four) and day 42 (week 6), data at day 42 (week 6) reported]

   This scale contains 14 items which yield two domain scores: dyadic sexual desire (DSD) and solitary sexual desire (SSD). Items 1,2, 10, 14 are 8-point Likert scale from '0' (= not at all) to '7' (= more than once a day) concerning frequency of desire. Remaining Items are 9-point Likert scale from '0' (= 'no desire') to '8' (= 'strong desire'). DSD has 8 items and SSD has 3 items. The total sores for DSD range from 0 to 62, and SSD, range from 0 to 23. All items are summed up to dictate the total sexual desire (total score = 0 to 112). Higher scores reflect higher sexual desire.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Had a diagnosis of opioid dependence base on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria

• While taking a stable dose of methadone In UMMC (University Malaya Medica Centre) and University Malaya centre of Addiction Science (UMCAS) outpatient clinic for ≥ 6 months

• Were experiencing constant sexual dysfunction for ≥ 4 weeks

• Were in a stable sexual relationship with a female partner for ≥ 6 months

Exclusion Criteria:

• Severe behavior disturbances or psychotic symptoms

• Obvious organic illnesses caused the sexual dysfunction (such as diabetics or patients with heart and vascular disease)

• Those with history of sexual dysfunction before methadone therapy

• Receiving antiviral treatment for viral hepatitis or HIV, or androgen replacement treatment.

• History of an eating disorder (eg, anorexia, bulimia) or seizures (eg, epilepsy)

• Using other psychotropic medications other than methadone

• Clinical significant abnormal laboratory values.

• Clinically significant abnormal ECG. Documented history of other psychiatric diagnosis (schizophrenia, bipolar disorder, major depressive disorder, organic brain disorder, dementia etc.)

• Refused to give participate.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Malaya Medical Center	Kuala Lumpur	Selangor	Malaysia	59100

Sponsors and Collaborators

• University of Malaya

Investigators

• Principal Investigator: Anne Yee, University Malaya Medical Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 1, 2015

More Information

Publications

None provided.

• Responsible Party: University of Malaya
• ClinicalTrials.gov Identifier: NCT02593396
• Other Study ID Numbers: AY001
• First Posted: Nov 1, 2015
• Last Update Posted: Aug 1, 2019
• Last Verified: Jul 1, 2019

• Keywords provided by University of Malaya: sexual dysfunctions; erectile dysfunctions; hypoactive sexual desire dysfunctions
• Additional relevant MeSH terms: Hypokinesia; Erectile Dysfunction; Sexual Dysfunctions, Psychological; Bupropion

Study Results

Participant Flow

Recruitment Details	All the male subjects who attended the methadone maintenance clinic from December 2015 to December 2017 in University Malaya Medical Center (UMMC) and University Malaya Center of Addiction Science Studies (UMCAS) were approached.Screening data was reviewed to determine subject eligibility.
Pre-assignment Detail	This study screened 109 and included 80 (73.4%) male patients who met all inclusion criteria and none of the exclusion criteria.

Arm/Group Title	Placebo	Active
Arm/Group Description	Placebo BD	Bupropion hydrochloride sustained-release 150mg BD
Period Title: Overall Study
STARTED	40	40
At Least Done One Efficacy Assessment	36	36
COMPLETED	25	26
NOT COMPLETED	15	14

Baseline Characteristics

Arm/Group Title	Placebo	Active	Total
Arm/Group Description	Placebo BD	Bupropion hydrochloride sustained-release 150mg BD	Total of all reporting groups
Overall Participants	40	40	80
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	43.50 (10.09)	42.30 (9.49)	42.83 (9.68)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	40 100%	40 100%	80 100%
Race/Ethnicity, Customized (Count of Participants)
Malay	34 85%	34 85%	68 85%
Chinese	5 12.5%	3 7.5%	8 10%
Indian	1 2.5%	1 2.5%	2 2.5%
Others	0 0%	2 5%	2 2.5%
Malay version of International Index of Erectile Function (Mal-IIEF-15) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	42.44 (16.43)	41.80 (19.13)	42.12 (17.78)
Total Malay version of the SDI-2 (SDI-2-BM) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	42.87 (15.83)	42.58 (14.97)	42.73 (15.4)

Outcome Measures

1. Primary Outcome

Title	Number of Participants With a Score of ≤2 (Much/Very Much Improved) on the Clinical Global Impression Scale Adapted for Sexual Function (CGI-SF) at Week 6 Between Placebo and Active Group
Description	This scale assesses the changes of the sexual function. Scores range from 1 (normal/very much improved) to 7 (most extreme sexual dysfunction/very much worse). Lower scores indicate better sexual functioning.
Time Frame	assessed at baseline, day 14(week 2), day 28(week four) and day 42 (week 6), data at day 42 (week 6) reported

Outcome Measure Data

Analysis Population Description

Intention-to-treat (ITT) analyses were used for all efficacy variables and included all patients who had been randomized, took at least 1 dose of study trial medication and had at least one efficacy assessment after the baseline visit. There were four patients in each arm did not come for first efficacy assessment, Hence, excluded from analysis.

Arm/Group Title	Placebo	Active
Arm/Group Description	Placebo BD	Bupropion hydrochloride sustained-release 150mg BD
Measure Participants	36	36
Count of Participants [Participants]	10 25%	21 52.5%

2. Secondary Outcome

Title	Mean Difference of Malay Version of International Index of Erectile Function (Mal-IIEF-15) at Week 6 Between Placebo and Active Group
Description	Mal-IIEF-15 is a 15-item, multi-dimensional self-reporting instrument for the evaluation of male sexual function for the past 4 weeks, consisted of five domains; 1) Erectile Function: sum of items 1, 2, 3, 4, 5 & 15. Total score range =1-30. 2) Orgasmic Function: sum of items 9 and 10. Total score range = 0 -10. 3) Sexual Desire: sum of items 11 and 12. Total score range = 2 -10. 4) Intercourse Satisfaction : sum of scores for Questions 6, 7 and 8. Total score range = 0 -15. 5) Overall Satisfaction: sum of items 13 and 14.Total score range = 2 -10. Items 1-10 is 6-point Likert-type scale from '0' (= No sexual activity) to '5' (= Almost always or always). Items 11-15 is 5-point Likert-type scale from '1' (= Almost never or never) to '5 '(= 'Almost always or always').The total Mal-IIEF-15 range from 5 (minimum) to 75 (Maximum). Higher score indicates better outcome in all domain.
Time Frame	assessed at baseline, day 14(week 2), day 28(week four) and day 42 (week 6), data at day 42 (week 6) reported

Outcome Measure Data

Analysis Population Description

Intention-to-treat (ITT) analyses were used for all efficacy variables and included all patients who had been randomized, took at least 1 dose of study trial medication and had at least one efficacy assessment after the baseline visit. There were four patients in each arm did not come for first efficacy assessment, Hence, excluded from analysis.

Arm/Group Title	Placebo	Active
Arm/Group Description	Placebo BD	Bupropion hydrochloride sustained-release 150mg BD
Measure Participants	36	36
IIEF total	43.81 (19.86)	52.53 (16.14)
Mal-IIEF-15, Erectile function domain	18.06 (9.43)	22.56 (7.69)
Mal-IIEF-15, Orgasmic function domain	5.99 (3.75)	7.30 (2.92)
Mal-IIEF-15, Sexual desire domain	6.04 (1.97)	6.77 (1.91)
Mal-IIEF-15, Intercourse satisfaction domain	6.46 (4.18)	8.78 (3.77)
Mal-IIEF-15, Overall satisfaction domain	7.14 (2.41)	7.10 (2.29)

3. Secondary Outcome

Title	Mean Difference of Malay Version of Sexual Desire Inventory 2 (SDI-2) Score at Weeks 6 Between Placebo and Active Groups
Description	This scale contains 14 items which yield two domain scores: dyadic sexual desire (DSD) and solitary sexual desire (SSD). Items 1,2, 10, 14 are 8-point Likert scale from '0' (= not at all) to '7' (= more than once a day) concerning frequency of desire. Remaining Items are 9-point Likert scale from '0' (= 'no desire') to '8' (= 'strong desire'). DSD has 8 items and SSD has 3 items. The total sores for DSD range from 0 to 62, and SSD, range from 0 to 23. All items are summed up to dictate the total sexual desire (total score = 0 to 112). Higher scores reflect higher sexual desire.
Time Frame	Assessed at baseline, day 14(week 2), day 28(week four) and day 42 (week 6), data at day 42 (week 6) reported

Outcome Measure Data

Analysis Population Description

Intention-to-treat (ITT) analyses were used for all efficacy variables and included all patients who had been randomized, took at least 1 dose of study trial medication and had at least one efficacy assessment after the baseline visit. There were four patients in each arm did not come for first efficacy assessment, Hence, excluded from analysis.

Arm/Group Title	Placebo	Active
Arm/Group Description	Placebo BD	Bupropion hydrochloride sustained-release 150mg BD
Measure Participants	36	36
SDI-2	47.36 (21.09)	53.53 (15.88)
DSD	29.99 (13.44)	36.08 (10.17)
SSD	6.87 (5.97)	7.45 (4.97)

Adverse Events

Time Frame	6 weeks
Adverse Event Reporting Description	patient self-report
Arm/Group Title	Placebo		Active
Arm/Group Description	Placebo BD		Bupropion hydrochloride sustained-release 150mg BD
All Cause Mortality
	Placebo		Active
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/36 (0%)		0/36 (0%)
Serious Adverse Events
	Placebo		Active
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/36 (0%)		0/36 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Active
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/36 (22.2%)		13/36 (36.1%)
Gastrointestinal disorders
constipation	2/36 (5.6%)	2	2/36 (5.6%)	2
nausea	2/36 (5.6%)	2	0/36 (0%)	0
General disorders
Insomnia	1/36 (2.8%)	1	6/36 (16.7%)	6
ineffectiveness	3/36 (8.3%)	3	0/36 (0%)	0
Psychiatric disorders
inability to concentrate	0/36 (0%)	0	2/36 (5.6%)	2
Skin and subcutaneous tissue disorders
skin rash	0/36 (0%)	0	3/36 (8.3%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.