Anorexia Nervosa, Anxiety, Depression, Eating Disorder
Conditions
Keywords
Testosterone, Hormones, Mental Health
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.
Interventions
DRUGTestosterone
Testosterone 300mcg transdermal patch x 24 weeks.
DRUGPlacebo
Placebo transdermal patch x 24 weeks
Sponsors
National Institute of Mental Health (NIMH)
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Weight | Baseline, 24 Weeks | Weight in kilograms |
| 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) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Testosterone Testosterone x 24 weeks
Testosterone: Testosterone 300mcg transdermal patch x 24 weeks.
Placebo: Placebo transdermal patch x 24 weeks | 43 |
| Placebo Placebo x 24 weeks
Testosterone: Testosterone 300mcg transdermal patch x 24 weeks.
Placebo: Placebo transdermal patch x 24 weeks | 47 |
| Total | 90 |
Baseline characteristics
| Characteristic | Placebo | Total | Testosterone |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 47 Participants | 90 Participants | 43 Participants |
| Age, Continuous | 27 years STANDARD_DEVIATION 7 | 27 years STANDARD_DEVIATION 7 | 28 years STANDARD_DEVIATION 7 |
| Region of Enrollment United States | 47 Participants | 90 Participants | 43 Participants |
| Sex: Female, Male Female | 47 Participants | 90 Participants | 43 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 43 | 0 / 47 |
| other Total, other adverse events | 33 / 43 | 33 / 47 |
| serious Total, serious adverse events | 4 / 43 | 1 / 47 |
Outcome results
Primary
Change From Baseline in Depression Symptom Severity
Hamilton Depression Rating Scale (HAM-D) (Higher score = greater depression symptom severity; Score Range 0 - ≥ 23)
Time frame: Baseline, 24 weeks
Population: All subjects who received at least one dose of study medication
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Testosterone | Change From Baseline in Depression Symptom Severity | -3 HAM-D score on a scale | Standard Deviation 5 |
| Placebo | Change From Baseline in Depression Symptom Severity | -3 HAM-D score on a scale | Standard Deviation 5 |
Primary
Change From Baseline in Weight
Weight in kilograms
Time frame: Baseline, 24 Weeks
Population: All subjects who received at least one dose of study medication
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Testosterone | Change From Baseline in Weight | 0.1 kilograms | Standard Deviation 2.7 |
| Placebo | Change From Baseline in Weight | 1.5 kilograms | Standard Deviation 3.2 |