Ignite Creation Date:
2024-05-06 @ 6:19 PM
Last Modification Date:
2024-10-26 @ 2:46 PM
Study NCT ID:
NCT05625555
Status:
RECRUITING
Last Update Posted:
2024-02-09
First Post:
2022-11-15
Brief Title:
Predictors of Intravenous Ketamine Response in TRD
Sponsor:
Abraham Nunes
Organization:
Nova Scotia Health Authority
Study Overview
Official Title:
Clinical Predictors of Intravenous Ketamine Response in Treatment-Resistant Depression A Randomized Double-Blind Midazolam-Controlled Pilot Study
Status:
RECRUITING
Status Verified Date:
2024-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
For patients with treatment-resistant depression TRD a single low dose of intravenous IV ketamine can help relieve symptoms as quickly as 24 hours later
The main problem with IV ketamine for TRD is that the effect is short-lived lasting only days to 1 or 2 weeks Furthermore IV ketamine is a resource-intensive treatment and the safety of long-term repeated use for depression is unknown To provide this treatment in a safe and cost-effective way Investigators must allocate it efficiently to those patients who have the greatest need and probability of benefit Therefore this project aims to find clinical features signs symptoms and parts of a patients history that will help predict which patients are most likely to respond to a single dose of IV ketamine for TRD This will help guide patient selection and triaging
Investigators will recruit 40 participants with TRD over one year and randomize them to one of two conditions ketamine followed by an active placebo 3-weeks later or vice versa With clinical data collected through detailed interviews questionnaires actigraphy speech sampling electroencephalography EEG and computerized tasks this study design will let us evaluate how well such factors predict A rapid response at 24-hours and B sustained response at 7 and 14 days
The main problem with IV ketamine for TRD is that the effect is short-lived lasting only days to 1 or 2 weeks Furthermore IV ketamine is a resource-intensive treatment and the safety of long-term repeated use for depression is unknown To provide this treatment in a safe and cost-effective way Investigators must allocate it efficiently to those patients who have the greatest need and probability of benefit Therefore this project aims to find clinical features signs symptoms and parts of a patients history that will help predict which patients are most likely to respond to a single dose of IV ketamine for TRD This will help guide patient selection and triaging
Investigators will recruit 40 participants with TRD over one year and randomize them to one of two conditions ketamine followed by an active placebo 3-weeks later or vice versa With clinical data collected through detailed interviews questionnaires actigraphy speech sampling electroencephalography EEG and computerized tasks this study design will let us evaluate how well such factors predict A rapid response at 24-hours and B sustained response at 7 and 14 days
Detailed Description:
Study Design
This will be a randomized double-blinded midazolam-controlled crossover trial There is no perfect control agent for studies of subanaesthetic IV ketamine but midazolam is generally thought to be superior to normal saline since it is not an antidepressant yet is psychoactive and thus should better preserve blinding Participants will undergo psychiatric assessment to establish diagnosis and determine suitability After providing informed consent for participation participants will wear a GENEActive accelerometer on the non-dominant wrist for the duration of the trial beginning 21 days prior to the first infusion Participants will complete a set of rating scales anhedonia measures and computerized tasks On Day 0 infusion day participants will receive either a single infusion of IV ketamine KET KET 05mgkg over 40 minutes or midazolam MID MID 30μgkg over 40 minutes diluted in 09 NaCl by an intravenous pump Investigators will randomize infusion sequences in a 1-to-1 ratio KET followed by MID KM or vice versa MK Infusions will be administered on Days 0 and 21 separated by a 20-day washout period This duration balances the need to establish comparable baselines at each crossover phase and the ethical consideration of not allowing depressive symptoms to remain untreated for an unreasonable amount of time
Investigators will obtain objective depression ratings with the Montgomery-Åsberg Depression Rating Scale MADRS on Days -1 1 7 14 20 22 28 35 and 41 Participants will provide weekly self-ratings of depressive symptoms using the Quick Inventory of Depressive Symptoms 16-item self-rated version QIDS 16-SR Weekly symptom monitoring will continue for 20 days following the second infusion Anhedonia will be measured using both self-reported rating scale measures as well as behavioural task Patients will provide self-ratings using the Snaith-Hamilton Pleasure Scale - 14 items SHAPS the Dimensional Anhedonia Rating Scale - 17 items DARS and Positive Valence System Scale - 21 items PVSS-21 Several aspects of subjective sleep and circadian rhythms will be measured via self-report questionnaires The Pittsburgh Sleep Quality Index PSQI will measure general sleep quality and sleep disturbance and the Basic Language Morningness Scale BALM will be used to measure subjective chronotype morningness-eveningness of patients Both will be completed by participants prior to the first infusion and 14 days after each infusion
Participants will complete the Epworth Sleepiness Scale ESS to measure daytime sleepiness symptoms as well as the Fatigue Scale Severity Scale FSS to measure symptoms of fatigue Both ESS and FSS will be completed the day before and after each infusion and every 7 days
Study Groups
Participants will receive either A 05mgkg of ketamine hydrochloride or B 30μgkg of MID diluted in 09 percent Sodium chloride NaCl over 40 minutes by an intravenous pump The KET and MID doses are similar to those used in previous studies and selected to minimize the possibility of unblinding Participants must abstain from consuming grapefruit juice or benzodiazepines for 24 hours preceding the infusion since the former is a potent CYP3A4 inhibitor that may reduce the rate of midazolam and ketamine elimination and the latter reduces the response to ketamine
This will be a randomized double-blinded midazolam-controlled crossover trial There is no perfect control agent for studies of subanaesthetic IV ketamine but midazolam is generally thought to be superior to normal saline since it is not an antidepressant yet is psychoactive and thus should better preserve blinding Participants will undergo psychiatric assessment to establish diagnosis and determine suitability After providing informed consent for participation participants will wear a GENEActive accelerometer on the non-dominant wrist for the duration of the trial beginning 21 days prior to the first infusion Participants will complete a set of rating scales anhedonia measures and computerized tasks On Day 0 infusion day participants will receive either a single infusion of IV ketamine KET KET 05mgkg over 40 minutes or midazolam MID MID 30μgkg over 40 minutes diluted in 09 NaCl by an intravenous pump Investigators will randomize infusion sequences in a 1-to-1 ratio KET followed by MID KM or vice versa MK Infusions will be administered on Days 0 and 21 separated by a 20-day washout period This duration balances the need to establish comparable baselines at each crossover phase and the ethical consideration of not allowing depressive symptoms to remain untreated for an unreasonable amount of time
Investigators will obtain objective depression ratings with the Montgomery-Åsberg Depression Rating Scale MADRS on Days -1 1 7 14 20 22 28 35 and 41 Participants will provide weekly self-ratings of depressive symptoms using the Quick Inventory of Depressive Symptoms 16-item self-rated version QIDS 16-SR Weekly symptom monitoring will continue for 20 days following the second infusion Anhedonia will be measured using both self-reported rating scale measures as well as behavioural task Patients will provide self-ratings using the Snaith-Hamilton Pleasure Scale - 14 items SHAPS the Dimensional Anhedonia Rating Scale - 17 items DARS and Positive Valence System Scale - 21 items PVSS-21 Several aspects of subjective sleep and circadian rhythms will be measured via self-report questionnaires The Pittsburgh Sleep Quality Index PSQI will measure general sleep quality and sleep disturbance and the Basic Language Morningness Scale BALM will be used to measure subjective chronotype morningness-eveningness of patients Both will be completed by participants prior to the first infusion and 14 days after each infusion
Participants will complete the Epworth Sleepiness Scale ESS to measure daytime sleepiness symptoms as well as the Fatigue Scale Severity Scale FSS to measure symptoms of fatigue Both ESS and FSS will be completed the day before and after each infusion and every 7 days
Study Groups
Participants will receive either A 05mgkg of ketamine hydrochloride or B 30μgkg of MID diluted in 09 percent Sodium chloride NaCl over 40 minutes by an intravenous pump The KET and MID doses are similar to those used in previous studies and selected to minimize the possibility of unblinding Participants must abstain from consuming grapefruit juice or benzodiazepines for 24 hours preceding the infusion since the former is a potent CYP3A4 inhibitor that may reduce the rate of midazolam and ketamine elimination and the latter reduces the response to ketamine
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None