Repeated Intranasal Esketamine Plus Almond Therapy in Patients With Treatment Resistant Depression (ZYL-730-01)

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

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

Study Overview

• Status: Terminated
• Conditions: Treatment Resistant Major Depressive Disorder
• Intervention / Treatment: Behavioral: Psychotherapy; Drug: Intranasal Ketamine (esketamine); Behavioral: Treatment as Usual

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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T5J 5C2
      • City Center Pharmacy and Medical Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Intranasal (esketamine) Ketamine with Addition of Almond therapy; Intranasal (esketamine) Ketamine - Dose of 56mg for a maximum of 2 weeks, followed by 56 mg or 84mg twice a week for a total of 8 doses during the 28 day study.	Behavioral: Psychotherapy; Participants will receive 8 remote therapy sessions conducted via phone or video, Therapy sessions consists of modules selected using a shared decision making process, tailored so that it is personally meaningful to each participant. Participants will also receive supportive text messages on selected days during the 28 day study.; Drug: Intranasal Ketamine (esketamine); Intranasal Ketamine (esketamine) - participants will receive a dose of 56 mg for a maximum of 2 weeks, followed by 56 mg or 84 twice a week for a total of 8 doses during the 28 -day study; Other Names: Spravato
Other: Intranasal (esketamine) Ketamine with Treatment as Usual; Intranasal (esketamine) Ketamine - Dose of 56 mg for a maximum of 2 weeks, followed by 56mg or 84mg twice a week for a total of 8 doses during the 28 day study.	Drug: Intranasal Ketamine (esketamine); Intranasal Ketamine (esketamine) - participants will receive a dose of 56 mg for a maximum of 2 weeks, followed by 56 mg or 84 twice a week for a total of 8 doses during the 28 -day study; Other Names: Spravato; Behavioral: Treatment as Usual; Participants will continue to receive the therapy that their treating physician felt was appropriate at the time of enrolment in the study, These can include cognitive behavioural therapy, supportive psychotherapy or mindfulness, support groups, physical exercise or relaxation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Montgomery Asberg Depression Rating Scale (MADRS) from screening to Day 28	The MADRS is a clinician rated 10-item scale where individuals score from 0-6 based on the severity of their symptoms, with higher scores indicative of greater severity	Screening, Day 7, 14, 21 and 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Post-traumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders (PCL-5)	A 20-item self-administered measure that assesses the presence and severity of PTSD symptoms. Participants will be asked to rate how bothered they have been by each itme in the past month on a 5-point Likert scale ranging from 0=Not at all to 4 = Extremely. The PCL-5 is easily scored by summing all of the items for a total symptom severity score ranging between 0-80. Clinically meaningful PTSD symptoms are present if items are rated as a minimum of 2 = "Moderate" or higher	Screening and Day 28
Change in Patient Health Questionnaire (PHQ-9)	A 9-item self-administered questionnaire to determine the presence and severity of depression which scores each of the 9 DSM-IV criteria as "0" ( not at all), to "3" ( nearly every day).	Screening, Day 2, 5, 9, 12,16, ,19, 23, 26 and 28
Change in Generalized Anxiety Disorder Questionnaire (GAD-7)	A 7- item self-administered questionnaire to measure the severity of the levels of anxiety. Each item can be score 0-3, giving a total score of 0-21.	Screening, Day 2, 5, 9, 12, 16, 19, 23, 26 and 28
Change in Rosenberg Self-Esteem Questionnaire (RSES)	A 10-item self-administered questionnaire to measure change in self esteem following psychological intervention. Each item scoring from 1-4, and higher scores indicating greater self-esteem	Screening and Day 28
Change in Quality of Life 8 Dimensional Questionnaire (AQoL-8D)	Self administered questionnaire measuring quality of life across 8 domains: independent living, happiness, mental health, coping, relationships, self-worth, pain and senses.	Screening and Day 28

Collaborators and Investigators

• Sponsor: Zylorion Health
• Investigators: Principal Investigator: Pierre Chue, MBBCh, Amygdala Associates

Study record dates

Study Major Dates

• Study Start (Actual): October 13, 2022
• Primary Completion (Actual): February 1, 2023
• Study Completion (Actual): February 1, 2023

Study Registration Dates

• First Submitted: March 24, 2022
• First Submitted That Met QC Criteria: April 4, 2022
• First Posted (Actual): April 12, 2022

Study Record Updates

• Last Update Posted (Actual): March 24, 2023
• Last Update Submitted That Met QC Criteria: March 22, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Psychotropic Drugs; Antidepressive Agents; Ketamine; Esketamine
• Other Study ID Numbers: HREBA-CTC-22-0015

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD will be available to other members of the research team including Dr. Craig Buchholz
• IPD Sharing Time Frame: Throughout the study.
• IPD Sharing Access Criteria: Involved in data collection
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No