Testosterone Antidepressant Augmentation in Women

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT01783574
• Collaborator: National Institutes of Health (NIH) (NIH), Lawley Pharmaceuticals (Industry)
• Enrollment: 101
• Locations: 2
• Arms: 2
• Actual Duration (Months): 41.9
• Patients Per Site: 50.5
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

The investigators' hypotheses are: Low-dose testosterone augmentation improves depressive symptoms in women with Major Depressive Disorder (MDD) and antidepressant partial/nonresponse, adjunctive low-dose testosterone is safe and well-tolerated in women with MDD and antidepressant partial/nonresponse, and low-dose testosterone augmentation improves fatigue and sexual dysfunction.

Condition or Disease	Intervention/Treatment	Phase
Depression	Drug: Testosterone; Drug: Placebo	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 101 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Collaborative Study: Testosterone Antidepressant Augmentation in Women
• Actual Study Start Date: Aug 1, 2013
• Actual Primary Completion Date: Jan 27, 2017
• Actual Study Completion Date: Jan 27, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Testosterone Testosterone cream will be applied to skin for 8 weeks. Starting dose is 10 mg daily and will be titrated based on blood levels.	Drug: Testosterone; Other Names: AndroFeme 1(testosterone 1% w/v cream)
Placebo Comparator: Placebo Placebo cream will appear identical to the testosterone cream and will be applied to skin for 8 weeks.	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. Depressive Symptom Severity [Week 8]

   Montgomery-Asberg Depression Rating Score (MADRS) Score: This scale measures depression symptom severity. Higher scores indicate more severe depression symptom severity. The score range is 0-60 units on a scale.

Secondary Outcome Measures

1. Fatigue [Week 8]

   Brief Fatigue Inventory: This inventory measures fatigue severity. Higher scores indicate more severe fatigue. The range is 0-10 units on a scale.

2. Sexual Dysfunction [Week 8]

   Derogatis Interview of Sexual Function (Total Score): This scale measures sexual function. Lower scores indicate worse sexual function. The score range for this questionnaire is 0-160.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 75 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Female, age 21-75

2. Major depressive disorder including MADRS>/=12

3. Currently treated with an antidepressant monotherapy (1st, 2nd or 3rd trial in current episode), that has been taken at an adequate dose for at least six weeks.

Exclusion Criteria:

1. Serious suicide or homicide risk, as assessed by evaluating clinician

2. Unstable medical illness including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic

3. Substance use disorder active within last six months, or clinical suspicion of ongoing substance use disorder at the discretion of the study clinician at time of screening based on history and/or laboratory results.

4. Any history of psychotic features, bipolar disorder, or primary obsessive compulsive disorder, as assessed by SCID

5. Currently treated with typical or atypical antipsychotic medications, or lithium

6. Untreated hypothyroidism. If treated hypothyroidism, change in levothyroxine dose within the prior 3 mos

7. Use of androgens, including testosterone, dehydroepiandrosterone (DHEA) and methyltestosterone, within the prior three months

8. Any investigational psychotropic drug within the last thirty days

9. In the judgment of the study clinician, unlikely to be able to participate safely throughout the study period (three or more episodes of self-harm in the past year, documented history of poor treatment adherence, or frequent missed appointments (>50%) in the past year)

10. ALT > 3x upper limit of normal or creatinine> 3x upper limit

11. History of a hormone-responsive cancer

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
2	Butler Hospital	Providence	Rhode Island	United States	02906

Sponsors and Collaborators

• Massachusetts General Hospital
• National Institutes of Health (NIH)
• Lawley Pharmaceuticals

Investigators

• Principal Investigator: Karen Miller, MD, Massachusetts General Hospital
• Principal Investigator: Maurizio Fava, MD, Massachusetts General Hospital
• Principal Investigator: Linda L Carpenter, MD, Butler Hospital

Study Documents (Full-Text)

• Study Protocol - May 19, 2017
• Statistical Analysis Plan - Feb 1, 2017

More Information

Publications

None provided.

• Responsible Party: Karen Klahr Miller, MD, Associate Professor of Medicine, Harvard Medical School, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT01783574
• Other Study ID Numbers: 2012D000537; R34MH09931501A1
• First Posted: Feb 5, 2013
• Last Update Posted: Jun 6, 2018
• Last Verified: May 1, 2018

• Keywords provided by Karen Klahr Miller, MD, Associate Professor of Medicine, Harvard Medical School, Massachusetts General Hospital: Depression; Major Depressive Disorder (MDD)
• Additional relevant MeSH terms: Depression; Methyltestosterone; Testosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate

Study Results

Participant Flow

Arm/Group Title	Testosterone	Placebo
Arm/Group Description	Testosterone cream will be applied to skin for 8 weeks. Starting dose is 10 mg daily and will be titrated based on blood levels. Testosterone	Placebo cream will appear identical to the testosterone cream and will be applied to skin for 8 weeks. Placebo
Period Title: Overall Study
STARTED	51	50
COMPLETED	46	41
NOT COMPLETED	5	9

Baseline Characteristics

Arm/Group Title	Testosterone	Placebo	Total
Arm/Group Description	Testosterone cream will be applied to skin for 8 weeks. Starting dose is 10 mg daily and will be titrated based on blood levels. Testosterone	Placebo cream will appear identical to the testosterone cream and will be applied to skin for 8 weeks. Placebo	Total of all reporting groups
Overall Participants	51	50	101
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46 (14)	48 (14)	47 (14)
Sex: Female, Male (Count of Participants)
Female	51 100%	50 100%	101 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	19 37.3%	21 42%	40 39.6%
Not Hispanic or Latino	32 62.7%	29 58%	61 60.4%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	1 2%	1 1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	5 10%	5 5%
White	51 100%	41 82%	92 91.1%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	3 6%	3 3%
Region of Enrollment (participants) [Number]
United States	51 100%	50 100%	101 100%
BMI (kg/m2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m2]	28.2 (7.6)	30.3 (7.9)	29.2 (7.8)
Mean MADRS Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	26.8 (6.3)	26.3 (5.4)	26.6 (5.9)
Postmenopausal (Count of Participants)
Count of Participants [Participants]	20 39.2%	26 52%	46 45.5%
Brief Fatigue Inventory (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	6.2 (1.9)	5.6 (2.0)	5.9 (2.0)
Derogatis Inventory of Sexual Function (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	32.8 (27.3)	38.7 (30.1)	35.7 (28.7)

Outcome Measures

1. Primary Outcome

Title	Depressive Symptom Severity
Description	Montgomery-Asberg Depression Rating Score (MADRS) Score: This scale measures depression symptom severity. Higher scores indicate more severe depression symptom severity. The score range is 0-60 units on a scale.
Time Frame	Week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Testosterone	Placebo
Arm/Group Description	Testosterone cream will be applied to skin for 8 weeks. Starting dose is 10 mg daily and will be titrated based on blood levels. Testosterone	Placebo cream will appear identical to the testosterone cream and will be applied to skin for 8 weeks. Placebo
Measure Participants	51	50
Mean (Standard Error) [units on a scale]	15.3 (1.4)	14.1 (1.4)

2. Secondary Outcome

Title	Fatigue
Description	Brief Fatigue Inventory: This inventory measures fatigue severity. Higher scores indicate more severe fatigue. The range is 0-10 units on a scale.
Time Frame	Week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Testosterone	Placebo
Arm/Group Description	Testosterone cream will be applied to skin for 8 weeks. Starting dose is 10 mg daily and will be titrated based on blood levels. Testosterone	Placebo cream will appear identical to the testosterone cream and will be applied to skin for 8 weeks. Placebo
Measure Participants	51	50
Mean (Standard Error) [units on a scale]	4.0 (0.3)	3.7 (0.4)

3. Secondary Outcome

Title	Sexual Dysfunction
Description	Derogatis Interview of Sexual Function (Total Score): This scale measures sexual function. Lower scores indicate worse sexual function. The score range for this questionnaire is 0-160.
Time Frame	Week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Testosterone	Placebo
Arm/Group Description	Testosterone cream will be applied to skin for 8 weeks. Starting dose is 10 mg daily and will be titrated based on blood levels. Testosterone	Placebo cream will appear identical to the testosterone cream and will be applied to skin for 8 weeks. Placebo
Measure Participants	51	50
Mean (Standard Error) [units on a scale]	45.1 (4.7)	47.5 (5.4)

Adverse Events

Time Frame	8 weeks
Adverse Event Reporting Description	Definition of serious adverse event is as defined on the clinicaltrials.gov website.
Arm/Group Title	Testosterone		Placebo
Arm/Group Description	Testosterone cream will be applied to skin for 8 weeks. Starting dose is 10 mg daily and will be titrated based on blood levels. Testosterone		Placebo cream will appear identical to the testosterone cream and will be applied to skin for 8 weeks. Placebo
All Cause Mortality
	Testosterone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/51 (0%)		0/50 (0%)
Serious Adverse Events
	Testosterone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/51 (0%)		0/50 (0%)
Other (Not Including Serious) Adverse Events
	Testosterone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/51 (29.4%)		13/50 (26%)
General disorders
Headache	6/51 (11.8%)		5/50 (10%)
Reproductive system and breast disorders
Hot flashes	2/51 (3.9%)		6/50 (12%)
Skin and subcutaneous tissue disorders
Acne	7/51 (13.7%)		3/50 (6%)

Limitations/Caveats

[Not Specified]

More Information

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.