AndroGel in Men With Major Depression and Incomplete Response to Antidepressant Treatment

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition	Depressive Disorder, Major
Interventions	Drug: Testosterone gel; Drug: Placebo
Enrollment	100

Participant Flow

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Recruitment Details	The study was conducted at two sites – McLean Hospital in Belmont Massachusetts, USA and the Chaim Sheba Medical Center in Tel Hashomer, Israel. Using advertisements at each site, we recruited men age 30-65 with major depressive disorder incompletely responsive to a serotonergic antidepressant, and showing a total testosterone level ≤ 350 ng/dL.
Pre-assignment Details	At baseline, participants began a 1-week, single-blind placebo lead-in of one packet of placebo gel daily. Men exhibiting ≥ 50% improvement on either the Hamilton Depression Rating Scale (HAM-D) or Montgomery-Asberg Depression Rating Scale (MADRS) after placebo lead-in were withdrawn; all others were randomized to study medication.

Arm/Group Title	Testosterone Gel	Placebo Gel
Arm/Group Description	AndroGel, (1% testosterone transdermal gel), 2.5 g - 10 g daily	Placebo gel identical in appearance to the testosterone gel
Period Title: Overall Study
Started	50	50
Completed	50	50
Not Completed	0	0

Baseline Characteristics

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Arm/Group Title		Testosterone Gel	Placebo Gel	Total
Arm/Group Description		AndroGel, (1% testosterone transdermal gel), 2.5 g - 10 g daily	Placebo gel identical in appearance to the testosterone gel	Total of all reporting groups
Overall Number of Baseline Participants		50	50	100
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	50 participants	50 participants	100 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	50 100.0%	50 100.0%	100 100.0%
	>=65 years	0 0.0%	0 0.0%	0 0.0%
Age Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	50 participants	50 participants	100 participants
		50.6 (8.2)	49.9 (7.1)	50.3 (7.7)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	50 participants	50 participants	100 participants
	Female	0 0.0%	0 0.0%	0 0.0%
	Male	50 100.0%	50 100.0%	100 100.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants	Number Analyzed	50 participants	50 participants	100 participants
United States		29	24	53
Israel		21	26	47

Outcome Measures

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1. Primary Outcome

Title	21-item Hamilton Depression Rating Scale Score (HAM-D)
Description	The HAM-D generates a score ranging from 0 (no depressive symptoms) to 64 (most severe depression).
Time Frame	9 weeks (1-week placebo lead-in and 8 weeks of blinded medication treatment)

Outcome Measure Data

Analysis Population Description

All of the 100 randomized participants are included in the Last Observation Carried Forward (LOCF) analysis presented here online, which provides the mean and SD of this outcome measure for each study arm. Full details of all analyses are provided in the published paper presenting the results of the study.

Arm/Group Title	Testosterone Gel	Placebo Gel
Arm/Group Description:	AndroGel, (1% testosterone transdermal gel), 2.5 g - 10 g daily	Placebo gel identical in appearance to the testosterone gel
Overall Number of Participants Analyzed	50	50
Mean (Standard Deviation); Unit of Measure: units on a scale
	13.5 (7.1)	15.6 (6.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Testosterone Gel, Placebo Gel
	Comments	Our primary analysis of efficacy was a mixed effects linear regression analysis comparing the rate of change of score on the HAM-D during the blinded treatment phase between groups. Our model for the mean of the outcome variable included terms for treatment, time (modeled as a continuous variable), and treatment-by-time. The measure of effect was the treatment-by-time interaction, which can be interpreted as the difference in slope with respect to time, of the outcome measure.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.71
	Comments	For a complete presentation of the above analysis, please see the published paper presenting the full results of this study.
	Method	mixed effects linear regression analysis
	Comments	[Not Specified]

2. Secondary Outcome

Title	Montgomery Asberg Depression Rating Scale (MADRS)
Description	The Montgomery Asberg Depression Rating Scale (MADRS) is a clinician-assessed scale that rates depressive symptoms on a scale from 0 (no depressive symptoms) to 60 (maximal depressive symptoms).
Time Frame	9 weeks (1 week of placebo lead-in and 8 weeks of blinded medication treatment)

Outcome Measure Data

Analysis Population Description

All of the 100 randomized participants are included in the Last Observation Carried Forward (LOCF) analysis presented here online, which provides the mean and SD of this outcome measure for each study arm. Full details of all analyses are provided in the published paper presenting the results of the study.

Arm/Group Title	Testosterone Gel	Placebo Gel
Arm/Group Description:	AndroGel, (1% testosterone transdermal gel), 2.5 g - 10 g daily	Placebo gel identical in appearance to the testosterone gel
Overall Number of Participants Analyzed	50	50
Mean (Standard Deviation); Unit of Measure: units on a scale
	17.9 (9.0)	19.9 (8.4)

Adverse Events

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Time Frame	Adverse events were assessed at all study visits throughout the eight-week blinded phase of the study.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Testosterone Gel		Placebo Gel
Arm/Group Description	AndroGel, (1% testosterone transdermal gel), 2.5 g - 10 g daily		Placebo gel identical in appearance to the testosterone gel
All-Cause Mortality
	Testosterone Gel		Placebo Gel
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Testosterone Gel		Placebo Gel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/50 (0.00%)		0/50 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Testosterone Gel		Placebo Gel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/50 (6.00%)		0/50 (0.00%)
Nervous system disorders
headache *	3/50 (6.00%)	3	0/50 (0.00%)	0
* Indicates events were collected by non-systematic assessment

Limitations and Caveats

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The small number of participants limited statistical power. Also, the study recruited “treatment-resistant” men, who are often poorly responsive. For a detailed discussion, see the published report of the study.

More Information

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/Title: Harrison G Pope Jr., M.D.

Organization: McLean Hospital

Phone: 617-855-2911

EMail: hpope@mcLean.harvard.edu

Publications of Results:

Pope HG Jr, Amiaz R, Brennan BP, Orr G, Weiser M, Kelly JF, Kanayama G, Siegel A, Hudson JI, Seidman SN. Parallel-group placebo-controlled trial of testosterone gel in men with major depressive disorder displaying an incomplete response to standard antidepressant treatment. J Clin Psychopharmacol. 2010 Apr;30(2):126-34. doi: 10.1097/JCP.0b013e3181d207ca.

Responsible Party:	Harrison G. Pope, Jr., M.D., McLean Hospital
ClinicalTrials.gov Identifier:	NCT00304746 History of Changes
Other Study ID Numbers:	2005P-001667
First Submitted:	March 16, 2006
First Posted:	March 20, 2006
Results First Submitted:	September 24, 2010
Results First Posted:	November 17, 2010
Last Update Posted:	November 24, 2010