NCT02487485

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
23

participants targeted

Target at below P25 for phase_2 depression

Timeline
Completed

Started Mar 2016

Typical duration for phase_2 depression

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 29, 2015

Completed
2 days until next milestone

First Posted

Study publicly available on registry

July 1, 2015

Completed
8 months until next milestone

Study Start

First participant enrolled

March 1, 2016

Completed
3.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2020

Completed
6 months until next milestone

Results Posted

Study results publicly available

July 7, 2020

Completed
Last Updated

July 16, 2020

Status Verified

July 1, 2020

Enrollment Period

3.8 years

First QC Date

June 29, 2015

Results QC Date

April 22, 2020

Last Update Submit

July 2, 2020

Conditions

Depression

Outcome Measures

Primary Outcomes (1)

  • Montgomery-Asberg Depression Rating Scale

    Montgomery-Asberg Depression Rating Scale (MADRS): The MADRS is a standardized instrument to ascertain depressed mood and neurovegetative signs and symptoms of depression. Ranges from 0-60 (higher is worse).

    Pretreatment and 2 week

Secondary Outcomes (6)

  • Quick Inventory of Depressive Symptoms (QIDS)

    Pretreatment and 2 week

  • Hamilton Anxiety Rating Scale (HAMA)

    Pretreatment and 2 week

  • Clinician Administered Dissociative States Scale (CADSS)

    During infusion, approximately 40 mins

  • Positive and Negative Symptom Scale (PANSS) - Positive

    During infusion, approximately 40 mins

  • Rapamycin Level

    During infusion, approximately 0 mins

  • +1 more secondary outcomes

Study Arms (2)

ketamine + sirolimus (placebo at time 2)

EXPERIMENTAL

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: KetamineDrug: sirolimusDrug: Placebo

ketamine + placebo (sirolimus at time 2)

PLACEBO COMPARATOR

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: KetamineDrug: sirolimusDrug: Placebo

Interventions

KetamineDRUG

. 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).

ketamine + placebo (sirolimus at time 2)ketamine + sirolimus (placebo at time 2)
sirolimusDRUG

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.

Also known as: Rapamune
ketamine + placebo (sirolimus at time 2)ketamine + sirolimus (placebo at time 2)
PlaceboDRUG

Placebo oral dose

ketamine + placebo (sirolimus at time 2)ketamine + sirolimus (placebo at time 2)

Eligibility Criteria

Age21 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Veterans and non-Veterans between the ages of 21-65.
  • Diagnosis of Major Depressive Episode (unipolar or bipolar) as determined by the Mini International Neuropsychiatric Interview (MINI).
  • Antidepressant-resistant depressive symptoms, defined by a history of failure of one or more adequate antidepressant trials.
  • 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.
  • Stable course of psychotherapy (if engaged in) for a period of four weeks or longer at the time of randomization.
  • 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.
  • Able to provide written informed consent according to VA HSS guidelines.
  • Ability to read and write in English.
  • A score greater than or equal to 18 on the Montgomery Ã…sberg Depression Rating Scale (MADRS).

You may not qualify if:

  • 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.
  • Current, ongoing serious suicidal risk as assessed by evaluating investigator or by scoring 5 or more on the item-10 of the MADRS.
  • Patients with unstable or inadequately controlled medical conditions.
  • Patient requiring prohibited medication.
  • Patient with history of organ transplant.
  • Meet criteria for a diagnosis of substance dependence (amphetamines, cocaine, hallucinogens, inhalants, opioids, sedatives/hypnotics/anxiolytics) within the three months prior to screening date.
  • Positive urine drug screen for cannabis, cocaine, PCP, or barbiturates.
  • Positive pregnancy test at screening at any screen given during the study.
  • Known sensitivity to sirolimus or ketamine.
  • History of sensitivity to heparin or heparin-induced thrombocytopenia.
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Yale New Haven Hospital

New Haven, Connecticut, 06511, United States

Location

West Haven Veterans Affairs

West Haven, Connecticut, 06516, United States

Location

MeSH Terms

Conditions

Depression

Interventions

KetamineSirolimus

Condition Hierarchy (Ancestors)

Behavioral SymptomsBehavior

Intervention Hierarchy (Ancestors)

CyclohexanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsMacrolidesLactones

Results Point of Contact

Title
Chadi Abdallah
Organization
Yale School of Medicine
chadi.abdallah@yale.edu
347-987-0717

Study Officials

  • Chadi Abdallah, MD

    Yale University

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
OTHER
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 29, 2015

First Posted

July 1, 2015

Study Start

March 1, 2016

Primary Completion

January 1, 2020

Study Completion

January 1, 2020

Last Updated

July 16, 2020

Results First Posted

July 7, 2020

Record last verified: 2020-07

Data Sharing

IPD Sharing
Will not share

Locations

US(2)