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Examining the Impact of Sirolimus on Ketamine's Antidepressant Effects

This study is currently recruiting participants.
See Contacts and Locations
Verified January 2017 by Yale University
Sponsor:
Information provided by (Responsible Party):
Yale University
ClinicalTrials.gov Identifier:
NCT02487485
First received: June 29, 2015
Last updated: January 5, 2017
Last verified: January 2017
  Purpose
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.

Condition Intervention Phase
Depression Drug: Ketamine Drug: sirolimus Drug: Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Official Title: Examining the Impact of Sirolimus on Ketamine's Antidepressant Effects

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • Depression as measured by Montgomery-Asberg Depression Rating Scale [ Time Frame: Baseline ]
    The MADRS is a standardized instrument to ascertain depressed mood and neurovegetative signs and symptoms of depression.

  • Depression as measured by Montgomery-Asberg Depression Rating Scale [ Time Frame: At infusion 1 ]
    The MADRS is a standardized instrument to ascertain depressed mood and neurovegetative signs and symptoms of depression.

  • Depression as measured by Montgomery-Asberg Depression Rating Scale [ Time Frame: 24 hours after infusion 1 ]
    The MADRS is a standardized instrument to ascertain depressed mood and neurovegetative signs and symptoms of depression.

  • Depression as measured by Montgomery-Asberg Depression Rating Scale [ Time Frame: 7 days after infusion 1 ]
    The MADRS is a standardized instrument to ascertain depressed mood and neurovegetative signs and symptoms of depression.

  • Depression as measured by Montgomery-Asberg Depression Rating Scale [ Time Frame: At Infusion 2 (14 days) ]
    The MADRS is a standardized instrument to ascertain depressed mood and neurovegetative signs and symptoms of depression.

  • Depression as measured by Montgomery-Asberg Depression Rating Scale [ Time Frame: 24 hours after infusion 2 (15 days) ]
    The MADRS is a standardized instrument to ascertain depressed mood and neurovegetative signs and symptoms of depression.

  • Depression as measured by Montgomery-Asberg Depression Rating Scale [ Time Frame: 7 days after infusion 2 (23+ days) ]
    The MADRS is a standardized instrument to ascertain depressed mood and neurovegetative signs and symptoms of depression.

  • Depression as measured by Montgomery-Asberg Depression Rating Scale [ Time Frame: 14 days after infusion 2 (30+ days) ]
    The MADRS is a standardized instrument to ascertain depressed mood and neurovegetative signs and symptoms of depression.


Estimated Enrollment: 30
Study Start Date: March 2016
Estimated Study Completion Date: August 2018
Estimated Primary Completion Date: August 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: 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).
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.
Other Name: Rapamune
Drug: Placebo
Placebo oral dose
Placebo Comparator: 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.
Drug: 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).
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.
Other Name: Rapamune
Drug: Placebo
Placebo oral dose

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

Ages Eligible for Study:   21 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02487485

Contacts
Contact: Prerana Purohit 203-932-5711 ext 5667 prerana.purohit@yale.edu
Contact: Lynnette A Averill, Ph.D. 203-932-5711 ext 5044 lynnette.averill@yale.edu

Locations
United States, Connecticut
Yale New Haven Hospital Not yet recruiting
New Have, Connecticut, United States, 06511
Contact: Chadi Abdullah, MD    347-987-0717    chadi.abdallah@yale.edu   
West Haven Veterans Affairs Recruiting
West Haven, Connecticut, United States, 06516
Contact: Prerana Purohit    203-932-5711 ext 5667    prerana.purohit@yale.edu   
Contact: Lynnette A Averill, Ph.D.    203-932-5711 ext 5044    lynnette.averill@yale.edu   
Sponsors and Collaborators
Yale University
Investigators
Principal Investigator: Chadi Abdallah, MD Yale University
  More Information

Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT02487485     History of Changes
Other Study ID Numbers: 1504015604
Study First Received: June 29, 2015
Last Updated: January 5, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Ketamine
Sirolimus
Everolimus
Antidepressive Agents
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Psychotropic Drugs

ClinicalTrials.gov processed this record on September 21, 2017