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Examining the Impact of Sirolimus on Ketamine's Antidepressant Effects

This study is currently recruiting participants.
Verified January 2017 by Yale University
Sponsor:
ClinicalTrials.gov Identifier:
NCT02487485
First Posted: July 1, 2015
Last Update Posted: January 9, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Yale University
June 29, 2015
July 1, 2015
January 9, 2017
March 2016
August 2018   (Final data collection date for primary outcome measure)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Complete list of historical versions of study NCT02487485 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Examining the Impact of Sirolimus on Ketamine's Antidepressant Effects
Examining the Impact of Sirolimus on Ketamine's Antidepressant Effects
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.

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.

Interventional
Phase 2
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Depression
  • 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
  • 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.
    Interventions:
    • Drug: Ketamine
    • Drug: sirolimus
    • Drug: Placebo
  • 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.
    Interventions:
    • Drug: Ketamine
    • Drug: sirolimus
    • Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
30
August 2018
August 2018   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: All
21 Years to 65 Years   (Adult)
No
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
United States
 
 
NCT02487485
1504015604
Yes
Not Provided
Plan to Share IPD: No
Yale University
Yale University
Not Provided
Principal Investigator: Chadi Abdallah, MD Yale University
Yale University
January 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP