Clinical trial NCT02487485: Examining the Impact of Sirolimus on Ketamine's Antidepressant Effects
Official title: Examining the Impact of Sirolimus on Ketamine's Antidepressant Effects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Depression
Lead sponsor: Yale University
Sponsor class: OTHER
First posted: 2015-07-01
Enrollment: 23
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: The aim of the study is to provide insight into the impact of the immunosuppressant drug sirolimus, on the antidepressant effects of the prototypal rapid-acting antidepressant medication, ketamine.

Detailed description: This is a double blind, placebo-controlled, crossover, randomized controlled trial investigating the impact of sirolimus on ketamine's antidepressant effects in participants with antidepressant-resistant depressive symptoms.

Prior to this, there was a phase 1 which included monitoring 3 subjects over the course of 7 days after a single dose of sirolimus and ketamine in order to inquire about side effects or interaction effects.

Eligibility criteria: Inclusion Criteria:

1. Veterans and non-Veterans between the ages of 21-65.
2. Diagnosis of Major Depressive Episode (unipolar or bipolar) as determined by the Mini International Neuropsychiatric Interview (MINI).
3. Antidepressant-resistant depressive symptoms, defined by a history of failure of one or more adequate antidepressant trials.
4. Stable doses of antidepressants (if prescribed) for a period of four weeks or longer at the time of randomization, except for MAOIs which are prohibited.
5. Stable course of psychotherapy (if engaged in) for a period of four weeks or longer at the time of randomization.
6. Females will be included if they are not pregnant or breastfeeding and agree to utilize a medically accepted birth control method (to include oral, injectable, or implant birth control, condom, diaphragm with spermicide, intrauterine device, tubal ligation, abstinence, or partner with vasectomy) or if post-menopausal for at least 1 year, or surgically sterile. For those women who are taking an oral contraceptive, we will also ask that they use (or ask their partners to use) a barrier method contraceptive.
7. Able to provide written informed consent according to VA HSS guidelines.
8. Ability to read and write in English.
9. A score greater than or equal to 18 on the Montgomery Åsberg Depression Rating Scale (MADRS).

Exclusion Criteria:

1. Subjects with a diagnostic history of schizophrenia or schizoaffective disorder, or currently exhibiting manic or mixed episodes or psychotic features as confirmed by the Mini International Neuropsychiatric Inventory.
2. Current, ongoing serious suicidal risk as assessed by evaluating investigator or by scoring 5 or more on the item-10 of the MADRS.
3. Patients with unstable or inadequately controlled medical conditions.
4. Patient requiring prohibited medication.
5. Patient with history of organ transplant.
6. Meet criteria for a diagnosis of substance dependence (amphetamines, cocaine, hallucinogens, inhalants, opioids, sedatives/hypnotics/anxiolytics) within the three months prior to screening date.
7. Positive urine drug screen for cannabis, cocaine, PCP, or barbiturates.
8. Positive pregnancy test at screening at any screen given during the study.
9. Known sensitivity to sirolimus or ketamine.
10. History of sensitivity to heparin or heparin-induced thrombocytopenia.
11. Resting blood pressure lower than 85/55 or higher than 150/95, or resting heart rate lower than 45/min or higher than 100/min.

Primary outcomes:
measure: Montgomery-Asberg Depression Rating Scale
timeFrame: Pretreatment and 2 week
Secondary outcomes:
measure: Quick Inventory of Depressive Symptoms (QIDS)
timeFrame: Pretreatment and 2 week
measure: Hamilton Anxiety Rating Scale (HAMA)
timeFrame: Pretreatment and 2 week
measure: Clinician Administered Dissociative States Scale (CADSS)
timeFrame: During infusion, approximately 40 mins
measure: Positive and Negative Symptom Scale (PANSS) - Positive
timeFrame: During infusion, approximately 40 mins
measure: Rapamycin Level
timeFrame: During infusion, approximately 0 mins
measure: Ketamine Level
timeFrame: During infusion, approximately 40 mins
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: West Haven
country: United States
facility: West Haven Veterans Affairs
state: Connecticut
Study officials:
affiliation: Yale University
name: Chadi Abdallah, MD
role: PRINCIPAL_INVESTIGATOR
References: