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Examining the Impact of Sirolimus on Ketamine's Antidepressant Effects

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02487485
Recruitment Status : Completed
First Posted : July 1, 2015
Last Update Posted : January 21, 2020
Sponsor:
Information provided by (Responsible Party):
Yale University

Tracking Information
First Submitted Date  ICMJE June 29, 2015
First Posted Date  ICMJE July 1, 2015
Last Update Posted Date January 21, 2020
Study Start Date  ICMJE March 2016
Actual Primary Completion Date January 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 25, 2019)
Montgomery-Asberg Depression Rating Scale [ Time Frame: Up to 2 weeks ]
The MADRS will assess depression severity
Original Primary Outcome Measures  ICMJE
 (submitted: June 29, 2015)
  • 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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 25, 2019)
  • Quick Inventory of Depressive Symptoms (QIDS) [ Time Frame: Up to 2 weeks ]
    The QIDS will assess depression severity
  • Hamilton Anxiety Rating Scale (HAMA) [ Time Frame: Up to 2 weeks ]
    The HAMA will assess severity of anxiety symptoms
  • Clinician Administered Dissociative States Scale (CADSS) [ Time Frame: During infusion ]
    The CADSS will assess the side effects of the study drug
  • Positive and Negative Symptom Scale (PANSS) [ Time Frame: During infusion ]
    The PANSS will assess the side effects of the study drug
  • Rapamycin level [ Time Frame: During infusion ]
    Plasma level
  • Ketamine level [ Time Frame: During infusion ]
    Plasma level
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Examining the Impact of Sirolimus on Ketamine's Antidepressant Effects
Official Title  ICMJE Examining the Impact of Sirolimus on Ketamine's Antidepressant Effects
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Other
Condition  ICMJE Depression
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Estimated Enrollment  ICMJE
 (submitted: March 9, 2016)
30
Original Estimated Enrollment  ICMJE
 (submitted: June 29, 2015)
45
Actual Study Completion Date  ICMJE January 2020
Actual Primary Completion Date January 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02487485
Other Study ID Numbers  ICMJE 1504015604
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Yale University
Study Sponsor  ICMJE Yale University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Chadi Abdallah, MD Yale University
PRS Account Yale University
Verification Date January 2020

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