Oral Aspirin + Ketamine as Adjunct to Oral Antidepressant Therapy for Depression

Study Overview
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Brief Summary
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The purpose of this study is to assess the effects of simultaneous administration of oral aspirin and oral ketamine as a therapeutic for those with Treatment Resistant Depression.

Detailed Description
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The objective of the study is to evaluate the effect of simultaneous administration of oral aspirin and oral ketamine, formulated for partial release in the oral cavity and partially swallowed, as an adjunct to the oral antidepressant on depressive symptoms in patients suffering from Treatment Resistant Depression (TRD) in outpatient Psychiatric Clinic. Investigators will evaluate the effects of simultaneous administration of oral aspirin and oral ketamine, on depressive symptoms. This is a prospective open-label, proof of concept clinical trial of simultaneous administration of proprietary formulations of oral aspirin and ketamine in medically stable adult patients with a diagnosis of Treatment Resistant Depression. All eligible participants will commit to three visits. The first two visits are in-person at the clinic for administration of oral ketamine and oral aspirin. Participants will be under observation for at least two hours. Study participant's vital signs will be monitored, periodically. The last visit will be conducted remotely. Adult patients 18 years of age and older, with a diagnosis of TRD presenting to the psychiatric clinic will be screened for enrollment by study team. :

Official Title
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An Open-Label Clinical Trial of Simultaneous Administration of Oral Aspirin and Ketamine as Adjunct to Oral Antidepressant Therapy in Treatment-Resistant Depression

Conditions
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Treatment Resistant Depression, Major Depressive Disorder, Analgesia, Ketamine, Peripheral Nervous System Agents, Central Nervous System Depressants, Neurotransmitter Agents, Anti-Inflammatory Agents, Physiological Effects of Drugs, Sensory System Agents, Analgesics, Non-Narcotic, Anti-Inflammatory Agents, Non-Steroidal, Depressive Symptoms

Intervention / Treatment
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* Drug: VTS-K


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients with Treatment Resistant Depression with Montgomery-Asberg Depression Rating Scale score >22 upon presentation to the clinic Treatment Resistant Depression is defined as Major Depressive Disorder that does not cease after at least 6 week trial of another class of antidepressants Unipolar Depression Exclusion Criteria: Adult patients with recent or current suicidal ideation with an intent to act, homicidal ideations with an intent to act History of Bipolar Disorder, Obsessive Compulsive Disorder, antisocial personality disorder, borderline personality disorder, and congestive cardiac failure Uncontrolled hypertension (BP >140 mm Hg systolic and/or >90 mm Hg diastolic on two separate readings at the time of screening) or on 2 medications for hypertension Patients with unstable vital signs (systolic blood pressure <90 or>160 mm Hg, pulse rate <50 or >150 beats/min, and respiration rate <10 or >30 breaths/min), History of Gastrointestinal hemorrhage, renal and hepatic insufficiency Allergy to Ketamine or Aspirin Active Substance Abuse Disorder Active psychosis Active Peptic Ulcer Disease Lithium Therapy Swallowing difficulty Consumption of Aspirin or NSAID's within 6 hours of arrival to the site Previous participation in this study; a patient may not re-enroll in another study while in this study Pregnant or breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 89 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Intervention Group<br>All individuals 18 years old or older who have Major Depressive Disorder and have failed to achieve response or remission to at least one proven antidepressant trial with minimum affective dose for a duration of at least 6 weeks. | Drug: VTS-K<br>* Proprietary oral formulation of 486mg aspirin and 80mg ketamine<br>* Other names: Ketamine + Aspirin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in depressive symptoms on the Montgomery-Åsberg Depression Rating Scale (MADRS). | Montgomery-Asberg Depression Rating Scale has a range from 0 to 60, where the lower score indicates the better health status. Change in mean total Montgomery Asberg Depression Rating Scale (MADRS) score from the baseline (pre-dose day 1 ) and on day 7 | 7 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A change in depressive symptoms on the Montgomery-Åsberg Depression Rating Scale (MADRS) from the baseline (pre-dose on day 1 and 4) and 2 hours post-medication administration | Montgomery-Asberg Depression Rating Scale has a range from 0 to 60, where the lower score indicates the better health status. Change in mean total Montgomery-Asberg Depression Rating Scale prior to dose administration on Day 1 and Day 4 compared to 2 hours after dose administration for each day. | 4 Days | 
| Clinician-Administered Dissociative States Scale (CADSS) | Measurement of dissociative symptoms. Clinician Administered Dissociative States Scale (CADSS) comprises 23 subjective items, each on a 5 point scale, a 0 represents absence of any adverse events and 4 represents a severely bothersome side effect. A total score ranges from 0-92, a lower score indicates a better health status. : | 4 Days | 
| Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) | Overall side effects as measured by the Side Effect Rating Scale for Dissociative Anesthetics (SERSDA). SERSDA has 9 items, each graded on a five point scale, with 0 representing the absence of any adverse effects and 4 representing a severely bothersome side effect. | 4 Days | 
| Maximal sedative effects using Modified Observer's Assessment of Alertness and Sedation ( MOAA/S) | Modified Observer's Alertness/Sedation Scale ( MOAA/S) uses a 6 point scale. A 0 indicates failure to respond to painful stimulus, 5 represents fully alert. . | 4 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Maimonides Medical Center, Psychiatry, Ketamine, Aspirin, Antipyretics, Peripheral Nervous System Agents, Sensory System Agents, NMDA receptor antagonist, Anesthetics, Dissociative, Excitatory Amino Acid Antagonists, Excitatory Amino Acid Agents, Cyclooxygenase Inhibitors, Oral Medications for depression