Hormonal Factors in the Treatment of Anorexia Nervosa

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT01121211
• Collaborator: National Institute of Mental Health (NIMH) (NIH)
• Enrollment: 90
• Location: 1
• Arms: 2
• Duration (Months): 70
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

The investigators are investigating whether a hormone that is naturally produced by the human body, called testosterone, can help improve weight, disordered eating, depression, and anxiety. The investigators hypothesize that testosterone will be a novel and effective endocrine-targeted therapy for patients with anorexia nervosa.

Condition or Disease	Intervention/Treatment	Phase
Anorexia Nervosa; Eating Disorder; Anxiety; Depression	Drug: Testosterone; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 90 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Hormonal Factors in the Treatment of Anorexia Nervosa
• Study Start Date: Apr 1, 2010
• Actual Primary Completion Date: Feb 1, 2016
• Actual Study Completion Date: Feb 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Testosterone Testosterone x 24 weeks	Drug: Testosterone; Testosterone 300mcg transdermal patch x 24 weeks.
Placebo Comparator: Placebo Placebo x 24 weeks	Drug: Placebo; Placebo transdermal patch x 24 weeks

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Weight [Baseline, 24 Weeks]

   Weight in kilograms

2. Change From Baseline in Depression Symptom Severity [Baseline, 24 weeks]

   Hamilton Depression Rating Scale (HAM-D) (Higher score = greater depression symptom severity; Score Range 0 - ≥ 23)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age 18- 45 years; if participating in the neuroimaging sub study, age 18-40

• Meet DSM-IV criteria for AN (restricting or binge/purge type, BMI 15-17.5) OR meet criteria for sub-threshold AN, i.e., all DSM-IV criteria except that patients can have a BMI of <18.5 kg/m2 with or without amenorrhea.

• Free T below the median for healthy women of reproductive age

• All participants will be required to have a treatment team in place that consists of (at least) a primary care physician and a psychotherapist. Participants will need to have had regular contact with a primary care physician and be in an individual psychotherapy program. Participants will agree to continue with this treatment team and therapy throughout the active course of the study. If participants are taking psychotropic medications, the dose must be stable for 3 months before study entry

Exclusion Criteria:

• Pregnant women or women of child bearing potential who are not using medically accepted means of contraception (to include oral contraceptive, patch or implant, condom, diaphragm, spermicide, intrauterine device, tubal ligation, or partner with vasectomy).

• Unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic

• Serious suicide risk, substance use disorder active within last 6 months, bipolar I disorder, severe current depressive symptoms (indexed by HAM-D score >20 [excluding 2 eating/weight loss items related to the symptoms of AN]), or psychotic disorder

• New psychotropic drug regimen, specifically a significant dose change or change in drug class, within the last 6 weeks. A study psychiatrist will assess whether PRN medications and dose changes are clinically significant enough to defer enrollment of specific potential study subjects.

• Untreated hypothyroidism

• If receiving estrogen therapy, including oral contraceptives or transdermal estrogen therapy, significant change in dose in the prior 3 months

• Use of androgens or androgen precursors, including T, DHEA and methyl T, within 3 months

• Any investigational psychotropic drug within the last 3 months

• In the judgment of the study clinician, unlikely to be able to participate safely throughout the study period

• Alanine aminotransferase (ALT) > 2x upper limit of normal

• Creatinine >1.5x upper limit

• Serum potassium < lower limit of normal

• If participating in the sub study, unable to tolerate 1 hour in MRI; contraindication to MRI (such as implanted pacemaker, cerebral aneurysm clips, extensive orthopedic hardware instrumentation); gastrointestinal tract surgery (including gastrectomy, gastric bypass surgery, and small or large bowel resection); history of psychosis by SCID

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02144

Sponsors and Collaborators

• Massachusetts General Hospital
• National Institute of Mental Health (NIMH)

Investigators

• Principal Investigator: Anne Klibanski, MD, Massachusetts General Hospital
• Study Director: Karen K Miller, MD, Massachusetts General Hospital
• Study Chair: Erinne Meenaghan, NP, Massachusetts General Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Karen Klahr Miller, MD, Chief, Neuroendocrine Unit, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT01121211
• Other Study ID Numbers: 2009P-001845/1; 5R01MH083657-05A2
• First Posted: May 12, 2010
• Last Update Posted: Sep 2, 2020
• Last Verified: Aug 1, 2020

• Keywords provided by Karen Klahr Miller, MD, Chief, Neuroendocrine Unit, Massachusetts General Hospital: Testosterone; Hormones; Mental Health
• Additional relevant MeSH terms: Anorexia; Feeding and Eating Disorders; Anorexia Nervosa; Testosterone

Study Results

Participant Flow

Arm/Group Title	Testosterone	Placebo
Arm/Group Description	Testosterone x 24 weeks Testosterone: Testosterone 300mcg transdermal patch x 24 weeks.	Placebo x 24 weeks Placebo: Placebo transdermal patch x 24 weeks
Period Title: Overall Study
STARTED	43	47
COMPLETED	32	35
NOT COMPLETED	11	12

Baseline Characteristics

Arm/Group Title	Testosterone	Placebo	Total
Arm/Group Description	Testosterone x 24 weeks Testosterone: Testosterone 300mcg transdermal patch x 24 weeks. Placebo: Placebo transdermal patch x 24 weeks	Placebo x 24 weeks Testosterone: Testosterone 300mcg transdermal patch x 24 weeks. Placebo: Placebo transdermal patch x 24 weeks	Total of all reporting groups
Overall Participants	43	47	90
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	43 100%	47 100%	90 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	28 (7)	27 (7)	27 (7)
Sex: Female, Male (Count of Participants)
Female	43 100%	47 100%	90 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	43 100%	47 100%	90 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Weight
Description	Weight in kilograms
Time Frame	Baseline, 24 Weeks

Outcome Measure Data

Analysis Population Description

All subjects who received at least one dose of study medication

Arm/Group Title	Testosterone	Placebo
Arm/Group Description	Testosterone x 24 weeks Testosterone: Testosterone 300mcg transdermal patch x 24 weeks. Placebo: Placebo transdermal patch x 24 weeks	Placebo x 24 weeks Testosterone: Testosterone 300mcg transdermal patch x 24 weeks. Placebo: Placebo transdermal patch x 24 weeks
Measure Participants	42	46
Mean (Standard Deviation) [kilograms]	0.1 (2.7)	1.5 (3.2)

2. Primary Outcome

Title	Change From Baseline in Depression Symptom Severity
Description	Hamilton Depression Rating Scale (HAM-D) (Higher score = greater depression symptom severity; Score Range 0 - ≥ 23)
Time Frame	Baseline, 24 weeks

Outcome Measure Data

Analysis Population Description

All subjects who received at least one dose of study medication

Arm/Group Title	Testosterone	Placebo
Arm/Group Description	Testosterone x 24 weeks Testosterone: Testosterone 300mcg transdermal patch x 24 weeks. Placebo: Placebo transdermal patch x 24 weeks	Placebo x 24 weeks Testosterone: Testosterone 300mcg transdermal patch x 24 weeks. Placebo: Placebo transdermal patch x 24 weeks
Measure Participants	42	46
Mean (Standard Deviation) [HAM-D score on a scale]	-3 (5)	-3 (5)

Adverse Events

Time Frame	24 weeks
Arm/Group Title	Testosterone		Placebo
Arm/Group Description	Testosterone x 24 weeks Testosterone: Testosterone 300mcg transdermal patch x 24 weeks.		Placebo x 24 weeks Placebo: Placebo transdermal patch x 24 weeks
All Cause Mortality
	Testosterone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/43 (0%)		0/47 (0%)
Serious Adverse Events
	Testosterone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/43 (9.3%)		1/47 (2.1%)
Gastrointestinal disorders
Hospitalization due to exacerbation of GI disorders	2/43 (4.7%)	2	0/47 (0%)	0
Psychiatric disorders
Hospitalization due to anorexia nervosa	1/43 (2.3%)	1	0/47 (0%)	0
Hospitalization due to depression exacerbation	1/43 (2.3%)	1	1/47 (2.1%)	1
Other (Not Including Serious) Adverse Events
	Testosterone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	33/43 (76.7%)		33/47 (70.2%)
Skin and subcutaneous tissue disorders
Acne or Increase in acne	14/43 (32.6%)	24	18/47 (38.3%)	24
Patch site irritation	12/43 (27.9%)	12	15/47 (31.9%)	15
Oily skin or Increase in oily skin	3/43 (7%)	3	2/47 (4.3%)	3
Hirsutism or Increased hair growth	9/43 (20.9%)	15	10/47 (21.3%)	15
Depilation	2/43 (4.7%)	2	4/47 (8.5%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.