Repeated Intranasal Esketamine Plus Almond Therapy in Participants With Treatment Resistant Depressive Disorder - 3 Month Extension Study

Phase 2

Withdrawn

• Conditions: Treatment Resistant Major Depressive Disorder
• Interventions: Behavioral: Almond Therapy; Behavioral: Treatment as Usual; Drug: Intranasal ketamine (Esketamine)

• Registration Number: NCT05438758
• Lead Sponsor: Zylorion Health

Brief Summary

The purpose of this study is to determine if any improvements in depressive symptoms are maintained in the medium and longer-term (up to 3 months)

Detailed Description

The duration of the study is 3 months

Participants enrolled in the Almond Therapy group will have up to 9 in person visits, including the baseline visits, participants will receive Esketamine on 8 of these visits. There are 12 remote therapy sessions conducted via telephone or video, participants will also receive supportive text messages. In addition, participants will have 4 telephone calls from an independent assessor to ask questions about their mental health (MADRS).

Participants enrolled in the Treatment as Usual group will have up to 9 in person visits, including the baseline visits, participants will receive Esketamine on 8 of these visits. Participants will continue to receive the therapy their treating physician felt was appropriate at the time of enrolment in the study. In addition, participants will have 4 telephone calls from an independent assessor to ask questions about their mental health (MADRS).

Participants will receive intranasal Esketamine 56mg or 84 mg once weekly for 4 weeks and 56 mg or 84 mg once every 2 weeks for 8 weeks as per Product Monograph

Study Timeline

• Study First Submitted: 2022-06-24
• Study First Submitted QC: 2022-06-24
• Study First Posted: 2022-06-30
• Status Verified: 2022-11
• Last Update Submitted: 2022-11-09
• Last Update Posted: 2022-11-15
• Study Start: 2023-01-15
• Primary Completion: 2024-02-01
• Study Completion: 2024-03-01

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. Participants must have completed Study ZYL-730-01 through to Day 28
2. Adults aged 18-64
3. Participants must have a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign an informed consent.
4. Women must use a medically acceptable reliable means of contraception and must agree to use adequate birth control for the duration of the study and for 6 weeks after the last dose using methods from the permitted list for contraception.
5. If currently receiving medication for depression their antidepressant dose(s) must be stable for the previous 4 weeks prior to baseline.
6. Must be on a stable dose of all other medication(s) for at least 1-month prior to baseline visit., unless medication is to treat other short term conditions (i.e. influenza, upper respiratory track infections, pain, etc.)
7. Controlled hypertension and must be on a stable dose of antihypertensive medications for at least 3 months prior to the baseline visit.

Exclusion Criteria

1. Women who plan to become pregnant, are pregnant or are breastfeeding.
2. Serious unstable medical illness, or any significant change in medical status at the baseline visit and during the study, as determined by the Investigator
3. Hormonal treatment (e.g., Estrogen) started within the 3 months prior to first dose of study treatment.
4. Participants who report treatment with a benzodiazepine, an opioid medication, or a mood stabilizer (such as valproic acid or lithium) at the baseline visit and within 2 weeks prior to the first dose of Esketamine .
5. Participants with confirmed psychotic disorder or symptoms, bipolar disorder and or clinically significant alcohol or substance misuse confirmed by a psychiatrist at the baseline visit. Those participants who develop symptoms of these may be withdrawn from the study, as determined by the Investigator
6. Current diagnosis of bulimia nervosa, or development of significant eating disorder symptoms at the baseline visit or during the study as determined by the Investigator
7. Participants who have been diagnosed with ADD/ADHD and who are also currently taking stimulant medication such as methylphenidate or another amphetamine-type medication, or who are diagnosed with this disorder or who start medication for this during the study.
8. Participants currently taking St John's Wort, Ginseng or Turmeric who start any of these during the study
9. Participants judged clinically to be actively at serious risk of self-harm or suicidal behaviour by the study team or psychiatrist at baseline or at any time during the study, as determined by the Investigator.
10. Blood pressure >140/90 at baseline
11. Participants who are unable to easily travel to the clinic for all of the in-person visits.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intranasal Esketamine with Addition of Almond TherapyTM	Almond Therapy	Intranasal Esketamine - Dose of 56 mg or 84 mg once a week for 4 weeks followed by 56 mg or 84 mg once every two weeks for 8 weeks.
Intranasal Esketamine with Treatment as Usual	Treatment as Usual	Intranasal Esketamine - Dose of 56 mg or 84 mg once a week for 4 weeks followed by 56 mg or 84 mg once every two weeks for 8 weeks.
Intranasal Esketamine with Addition of Almond TherapyTM	Intranasal ketamine (Esketamine)	Intranasal Esketamine - Dose of 56 mg or 84 mg once a week for 4 weeks followed by 56 mg or 84 mg once every two weeks for 8 weeks.
Intranasal Esketamine with Treatment as Usual	Intranasal ketamine (Esketamine)	Intranasal Esketamine - Dose of 56 mg or 84 mg once a week for 4 weeks followed by 56 mg or 84 mg once every two weeks for 8 weeks.

Primary Outcome Measures

Name	Time	Method
Change in Montgomery Asberg Depression Rating Scale (MADRS)	Baseline, Day 26, 54 and 89	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

Secondary Outcome Measures

Name	Time	Method
Change in Rosenberg Self-Esteem Questionnaire (RSES)	Baseline, Day 26, 54 and 82	A 10-item self administered questionnaire to measure change in self esteem following psychological intervention. Each item scoring from 1-4, and higher scores indication greater self-esteem
Change in Quality of Life 8 Dimensional Questionnaire (AQoL-8D)	Baseline, Day 26, 54 and 82	Self administered questionnaire measuring quality of life across 8 domains: independent living, happiness, mental health, coping, relationships, self-worth, pain and senses
Change in Post-Traumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders (PCL-5	Baseline, Day 26, 54 and 82	A 20-item self-administered measure that assesses the presence and severity of PTSD symptoms derived from the symptoms of PTSD in DSM-5. Participants will be asked to rate how bothered they have been by each item in the 4 weeks 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.
Change in Patient Health Questionnaire (PHQ-9)	Baseline, Day 12, 26, 40, 54, 68 and 82	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 everyday
Change in Generalized Anxiety Disorder Questionnaire (GAD-7)	Baseline, Day 12, 26, 40, 54, 68 and 82	A 7-item self-administered questionnaire to measure the severity of the levels of anxiety. Each item can be scored 0-3, giving a total score of 0-21.