Examining the Impact of Sirolimus on Ketamine’s... — Clinical Trial Details

This double-blind, randomized crossover study (n=23) evaluates whether sirolimus (6 mg oral) modifies the acute and short-term antidepressant effects of ketamine (0.5 mg/kg IV infused over ~40 minutes), with each participant receiving two ketamine infusions separated by two weeks.

Primary population includes adults 21–65 with antidepressant-resistant major depressive episodes; outcomes include MADRS change and safety/tolerability, with sirolimus/placebo administered ~2 hours prior to infusions.

Participants

Ages

21 – 65

Sexes

Male & Female

BMI

Psychosis History

Inclusion 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 utilise 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

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.

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Examining the Impact of Sirolimus on Ketamine’s Antidepressant Effects

Detailed Description

Study Protocol

Preparation

Dosing

Locations

Related Publications

Modulation of the antidepressant effects of ketamine by the mTORC1 inhibitor rapamycin

Integration

Study Arms & Interventions

Ketamine + Sirolimus

Interventions

Ketamine + Placebo

Interventions

Participants

Inclusion Criteria

Exclusion Criteria

Study Details

Study Team

Sponsors & Collaborators