Clinical trial NCT05323019: Repeated Intranasal Esketamine Plus Almond Therapy in Patients With Treatment Resistant Depression
Official title: A Randomized, Controlled, Single-Blind, Phase 2 Study in Treatment Resistant Major Depressive Disorder Patients Receiving Intranasal Esketamine (SpravatoTM) Over a 28-day Period Comparing Addition of Almond TherapyTM With Treatment-as-Usual
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Treatment Resistant Major Depressive Disorder
Lead sponsor: Zylorion Health
Sponsor class: INDUSTRY
First posted: 2022-04-12
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized by a pre-specified block design method after confirming eligibility.
Primary purpose: TREATMENT

Brief summary: To examine the efficacy of Almond Therapy compared to Treatment as Usual when used in addition to an approved version of intranasal esketamine.

Detailed description: The duration of the study is 28 days.

Participants enrolled in the Almond Therapy arm will have up 10 in person clinic visits, including the screening visit, participants will receive esketamine on 8 of these visits. There are also 8 remote therapy sessions conducted via telephone or video, and participants will also receive supportive text messages. Participants will have 5 telephone calls from an independent assessor to ask questions about their mental health (MADRS).

Participants enrolled in the Treatment as usual will have 10 in-person clinic visits, including the Screening visit, participants will receive intranasal esketamine on 8 of these visits. Participants will continue to receive the therapy that their treating physician felt was appropriate at the time of enrolment in the study. In addition, participants will have 5 telephone calls from an independent assessor to ask questions on their mental health ( MADRS).

Participants will receive intranasal esketamine twice-weekly according to the Product Monograph. To ensure that both groups receive approximately equal amounts of esketamine, patients will receive 56mg initially for a maximum of 2 weeks followed by 56mg or 84mg. As per the Product Monograph these will be given for 4 weeks for a total of 8 doses during the 28-day study.

Eligibility criteria: Inclusion Criteria:

* Score on MADRS scale with a score of 18 or greater
* Meet criteria for Treatment-Resistant Major Depressive Disorder, defined as having not responded adequately to at least two separate courses of treatment with different antidepressant at an adequate dose and duration in the current moderate to severe depression episode, as determined by an appropriately trained psychiatrist.
* Women of child bearing potential must use a medically acceptable means of contraception for the duration of the study and for 6 weeks after the last dose of esktamine.
* Negative blood pregnancy test prior to baseline
* If currently receiving medication for depression, antidepressant dose must be stable for the previous 4 weeks prior to baseline.
* Stable dose of all other medication for at least 1 month prior to baseline
* Controlled hypertension and on a stable dose of antihypertension medications for at least 3 months prior to baseline visit

Exclusion Criteria:

* Women who plan to become pregnant, are pregnant or are breastfeeding
* Serious unstable medical illness as determined by the Investigator.
* Participants with uncontrolled hypothyroidism and hyperthyroidism
* Hormonal treatment (e.g., Estrogen) started within the 3 months prior to first dose of study treatment.
* Participants who report treatment with a benzodiazepine, an opioid medication, or a mood stabilizer (such as valproic acid or lithium) within 2 weeks prior to the first dose of esketamine.
* Participants with confirmed psychotic disorder or symptoms, bipolar disorder and or clinically significant alcohol or substance misuse confirmed by a psychiatrist in the previous 2 years.
* Previous ketamine abuse as determined by Investigator
* Previous non-response to clinical or research ketamine administration
* Current diagnosis of bulimia nervosa
* Participants who have been diagnosed with ADD/ADHD and who are also currently taking stimulant medication such as methylphenidate or another amphetamine-type medication.
* Participants currently taking St John's Wort, Ginseng or Turmeric
* Participants judged clinically to be actively at serious risk of self-harm or suicidal behaviour by the study team or psychiatrist at Screening.
* Blood pressure \>140/90 at screening

Primary outcomes:
measure: Change in the Montgomery Asberg Depression Rating Scale (MADRS) from screening to Day 28
timeFrame: Screening, Day 7, 14, 21 and 28
Secondary outcomes:
measure: Change in Post-traumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders (PCL-5)
timeFrame: Screening and Day 28
measure: Change in Patient Health Questionnaire (PHQ-9)
timeFrame: Screening, Day 2, 5, 9, 12,16, ,19, 23, 26 and 28
measure: Change in Generalized Anxiety Disorder Questionnaire (GAD-7)
timeFrame: Screening, Day 2, 5, 9, 12, 16, 19, 23, 26 and 28
measure: Change in Rosenberg Self-Esteem Questionnaire (RSES)
timeFrame: Screening and Day 28
measure: Change in Quality of Life 8 Dimensional Questionnaire (AQoL-8D)
timeFrame: Screening and Day 28
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: City Center Pharmacy and Medical Clinic
state: Alberta
Study officials:
affiliation: Amygdala Associates
name: Pierre Chue, MBBCh
role: PRINCIPAL_INVESTIGATOR
References: