Examining the Impact of Sirolimus on Ketamine's Antidepressant Effects

NCT ID: NCT02487485

Last Updated: 2020-07-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-31
• Study Completion Date: 2020-01-31

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.

Conditions

Depression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: TRIPLE

Study Groups

ketamine + sirolimus (placebo at time 2)

Participants will be treated twice with ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of sirolimus 6 mg orally. After two weeks, they will recieve another infusion of ketamine, and a single dose of placebo.

Group Type: EXPERIMENTAL

Ketamine

Intervention Type: DRUG

. Subjects will receive an infusion of ketamine (0.5 mg/kg infusion over approximately 40 minutes). All subjects will receive two ketamine infusions-once with a placebo and once with a single dose of sirolimus (6 mg, oral administration).

sirolimus

Intervention Type: DRUG

Subjects will receive a single 6 mg oral dose via oral solution of sirolimus or a dose of placebo approximately two hours prior to the infusions. As above, the order of placebo and sirolimus is randomized. The sirolimus dose as well as the placebo solution will be given in 6 ounces of orange juice.

Placebo

Intervention Type: DRUG

Placebo oral dose

ketamine + placebo (sirolimus at time 2)

Participants will be treated twice with ketamine 0.5 mg/kg infused over 40 minutes, combined with a single dose of sirolimus 6 mg placebo. After two weeks, they will recieve another infusion of ketamine, and a single dose of sirolimus 6 mg.

Group Type: PLACEBO_COMPARATOR

Ketamine

Intervention Type: DRUG

. Subjects will receive an infusion of ketamine (0.5 mg/kg infusion over approximately 40 minutes). All subjects will receive two ketamine infusions-once with a placebo and once with a single dose of sirolimus (6 mg, oral administration).

sirolimus

Intervention Type: DRUG

Subjects will receive a single 6 mg oral dose via oral solution of sirolimus or a dose of placebo approximately two hours prior to the infusions. As above, the order of placebo and sirolimus is randomized. The sirolimus dose as well as the placebo solution will be given in 6 ounces of orange juice.

Placebo

Intervention Type: DRUG

Placebo oral dose

Interventions

Ketamine

. Subjects will receive an infusion of ketamine (0.5 mg/kg infusion over approximately 40 minutes). All subjects will receive two ketamine infusions-once with a placebo and once with a single dose of sirolimus (6 mg, oral administration).

Intervention Type: DRUG

sirolimus

Subjects will receive a single 6 mg oral dose via oral solution of sirolimus or a dose of placebo approximately two hours prior to the infusions. As above, the order of placebo and sirolimus is randomized. The sirolimus dose as well as the placebo solution will be given in 6 ounces of orange juice.

Intervention Type: DRUG

Placebo

Placebo oral dose

Intervention Type: DRUG

Other Intervention Names

Rapamune

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.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Chadi Abdallah, MD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

Yale New Haven Hospital

New Haven, Connecticut, United States

West Haven Veterans Affairs

West Haven, Connecticut, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

1504015604

Identifier Type: -

Identifier Source: org_study_id