DepressionPhase 2NCT02487485
Examining the Impact of Sirolimus on Ketamine's Antidepressant Effects
A Phase 2 study testing Ketamine and sirolimus in people with Depression, run by Yale University at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 65 years
- Conditions the study is for
- Depression
- What is being tested?
- Ketamine and sirolimus
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 23 participants
- Where
- 2 sitesUnited States
- Study dates
- Mar 2016to Jan 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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 Åsberg Depression Rating Scale (MADRS).
Who cannot join
- 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.
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- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Yale New Haven Hospital
New Haven, Connecticut, 06511
West Haven Veterans Affairs
West Haven, Connecticut, 06516
About this study
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.
Read the 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
- Medical subject headings
- Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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).
sirolimusDrug
Also called Rapamune
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.
PlaceboDrug
Placebo oral dose
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Ketamine; Drug: sirolimus; Drug: 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. Receives: Drug: Ketamine; Drug: sirolimus; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Pretreatment and 2 week
Secondary outcomes (6)
Quick Inventory of Depressive Symptoms (QIDS)
Quick Inventory of Depressive Symptoms - Self-Report (QIDS-SR): The QIDS-SR is a patient-rated depression instrument. Ranges from 0-27 (higher is worse).
Measured: Pretreatment and 2 week
Hamilton Anxiety Rating Scale (HAMA)
Hamilton Anxiety Rating Scale (HAM-A): The HAM-A is a standardized clinician-rated instrument to evaluate the severity of anxiety symptoms. Ranges from 0-56 (higher is worse).
Measured: Pretreatment and 2 week
Clinician Administered Dissociative States Scale (CADSS)
Clinician Administered Dissociative States Scale (CADSS): The CADSS has self and interviewer-administered items including 5 subscales, generated a priori, evaluating dissociation including altered environmental perception, time perception, spatial/body perception, derealization and memory impairment. Ranges from 0-108 (higher is worse).
Measured: During infusion, approximately 40 mins
Positive and Negative Symptom Scale (PANSS) - Positive
Positive and Negative Symptom Scale (PANSS): The PANSS is commonly used to measure the severity of symptoms in psychotic disorders. It is a clinician- administered scale and includes three categories of symptoms: (1) positive symptoms, such as hallucination and delusion; (2) negative symptoms, such as flat affect and difficulty in abstract thinking; (3) general psychopathology, such as mannerisms and posturing. Ranges from 0-49 for positive scale (higher is worse).
Measured: During infusion, approximately 40 mins
Rapamycin Level
Plasma level of rapamycin (a.k.a. sirolimus).
Measured: During infusion, approximately 0 mins
Ketamine Level
Plasma level of ketamine
Measured: During infusion, approximately 40 mins
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2015 (estimated)
- Study startMar 2016
- Primary completionJan 2020
- Study completionJan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for DepressionStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Chadi Abdallah, MD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02487485
- Sponsor's protocol ID
- 1504015604
- Status last verified
- Jul 2020
- First submitted
- 29 Jun 2015
- Last updated
- 16 Jul 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Examining the Impact of Sirolimus on Ketamine's Antidepressant Effects
- ClinicalTrials.gov ID
- NCT02487485
- Acronym / sponsor ID
- 1504015604
- Conditions
- Depression
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Study start
- Mar 2016
- Primary completion
- Jan 2020 (actual)
- Study completion
- Jan 2020 (actual)
- First posted
- 1 Jul 2015 (estimated)
- Results
- Posted 7 Jul 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ketamine + sirolimus (placebo at time 2) | Experimental | Drug: Ketamine, Drug: sirolimus, Drug: PlaceboParticipants 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. |
| ketamine + placebo (sirolimus at time 2) | Placebo comparator | Drug: Ketamine, Drug: sirolimus, Drug: PlaceboParticipants 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. |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | ketamine + placebo (sirolimus at time 2), ketamine + sirolimus (placebo at time 2) |
| sirolimusAlso: RapamuneSubjects 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. | Drug | ketamine + placebo (sirolimus at time 2), ketamine + sirolimus (placebo at time 2) |
| PlaceboPlacebo oral dose | Drug | ketamine + placebo (sirolimus at time 2), ketamine + sirolimus (placebo at time 2) |
Primary outcome
Montgomery-Asberg Depression Rating Scale
Time frame: Pretreatment and 2 week
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).
6 secondary outcomes
Quick Inventory of Depressive Symptoms (QIDS)
Time frame: Pretreatment and 2 week
Hamilton Anxiety Rating Scale (HAMA)
Time frame: Pretreatment and 2 week
Clinician Administered Dissociative States Scale (CADSS)
Time frame: During infusion, approximately 40 mins
Positive and Negative Symptom Scale (PANSS) - Positive
Time frame: During infusion, approximately 40 mins
Rapamycin Level
Time frame: During infusion, approximately 0 mins
Ketamine Level
Time frame: During infusion, approximately 40 mins
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jul 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chadi Abdallah, MD principal investigator
Yale University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ketamine and sirolimus in people with Depression, run by Yale University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Montgomery-Asberg Depression Rating Scale (time frame: Pretreatment and 2 week). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jul 2020.