Hormonal Factors in the Treatment of Anorexia Nervosa

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.

Study Overview

• Status: Completed
• Conditions: Depression; Anorexia Nervosa; Anxiety; Eating Disorder
• Intervention / Treatment: Drug: Testosterone; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02144
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Study Director: Karen K Miller, MD, Massachusetts General Hospital

Publications and helpful links

General Publications

• Kimball A, Schorr M, Meenaghan E, Bachmann KN, Eddy KT, Misra M, Lawson EA, Kreiger-Benson E, Herzog DB, Koman S, Keane RJ, Ebrahimi S, Schoenfeld D, Klibanski A, Miller KK. A Randomized Placebo-Controlled Trial of Low-Dose Testosterone Therapy in Women With Anorexia Nervosa. J Clin Endocrinol Metab. 2019 Oct 1;104(10):4347-4355. doi: 10.1210/jc.2019-00828.

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): February 1, 2016

Study Registration Dates

• First Submitted: May 10, 2010
• First Submitted That Met QC Criteria: May 11, 2010
• First Posted (Estimate): May 12, 2010

Study Record Updates

• Last Update Posted (Actual): September 2, 2020
• Last Update Submitted That Met QC Criteria: August 31, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Mental Health; Testosterone; Hormones
• Additional Relevant MeSH Terms: Mental Disorders; Signs and Symptoms, Digestive; Anorexia; Anorexia Nervosa; Feeding and Eating Disorders; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Androgens; Testosterone
• Other Study ID Numbers: 2009P-001845/1; 5R01MH083657-05A2 (U.S. NIH Grant/Contract)