Clinical trial NCT05615948: Oral Aspirin + Ketamine as Adjunct to Oral Antidepressant Therapy for Depression
Official title: An Open-Label Clinical Trial of Simultaneous Administration of Oral Aspirin and Ketamine as Adjunct to Oral Antidepressant Therapy in Treatment-Resistant Depression
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: 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
Keywords: 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
Lead sponsor: Maimonides Medical Center
Sponsor class: OTHER
First posted: 2022-11-14
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

:

Eligibility criteria: 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

Primary outcomes:
measure: Change in depressive symptoms on the Montgomery-Åsberg Depression Rating Scale (MADRS).
timeFrame: 7 Days
Secondary outcomes:
measure: 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
timeFrame: 4 Days
measure: Clinician-Administered Dissociative States Scale (CADSS)
timeFrame: 4 Days
measure: Side Effect Rating Scale for Dissociative Anesthetics (SERSDA)
timeFrame: 4 Days
measure: Maximal sedative effects using Modified Observer's Assessment of Alertness and Sedation ( MOAA/S)
timeFrame: 4 Days
Other outcomes:
Locations:
city: Brooklyn
country: United States
facility: Maimonides Medical Center
state: New York
Study officials:
affiliation: Maimonides Medical Center
name: Deepan Singh, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Daly EJ, Trivedi MH, Janik A, Li H, Zhang Y, Li X, Lane R, Lim P, Duca AR, Hough D, Thase ME, Zajecka J, Winokur A, Divacka I, Fagiolini A, Cubala WJ, Bitter I, Blier P, Shelton RC, Molero P, Manji H, Drevets WC, Singh JB. Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression: A Randomized Clinical Trial. JAMA Psychiatry. 2019 Sep 1;76(9):893-903. doi: 10.1001/jamapsychiatry.2019.1189.
citation: Wajs E, Aluisio L, Holder R, Daly EJ, Lane R, Lim P, George JE, Morrison RL, Sanacora G, Young AH, Kasper S, Sulaiman AH, Li CT, Paik JW, Manji H, Hough D, Grunfeld J, Jeon HJ, Wilkinson ST, Drevets WC, Singh JB. Esketamine Nasal Spray Plus Oral Antidepressant in Patients With Treatment-Resistant Depression: Assessment of Long-Term Safety in a Phase 3, Open-Label Study (SUSTAIN-2). J Clin Psychiatry. 2020 Apr 28;81(3):19m12891. doi: 10.4088/JCP.19m12891.
citation: Ochs-Ross R, Daly EJ, Zhang Y, Lane R, Lim P, Morrison RL, Hough D, Manji H, Drevets WC, Sanacora G, Steffens DC, Adler C, McShane R, Gaillard R, Wilkinson ST, Singh JB. Efficacy and Safety of Esketamine Nasal Spray Plus an Oral Antidepressant in Elderly Patients With Treatment-Resistant Depression-TRANSFORM-3. Am J Geriatr Psychiatry. 2020 Feb;28(2):121-141. doi: 10.1016/j.jagp.2019.10.008. Epub 2019 Oct 17.
citation: Ketterer MW, Brymer J, Rhoads K, Kraft P, Lovallo WR. Is aspirin, as used for antithrombosis, an emotion-modulating agent? J Psychosom Res. 1996 Jan;40(1):53-8. doi: 10.1016/0022-3999(95)00524-2.
citation: Mendlewicz J, Kriwin P, Oswald P, Souery D, Alboni S, Brunello N. Shortened onset of action of antidepressants in major depression using acetylsalicylic acid augmentation: a pilot open-label study. Int Clin Psychopharmacol. 2006 Jul;21(4):227-31. doi: 10.1097/00004850-200607000-00005.
citation: Ng QX, Ramamoorthy K, Loke W, Lee MWL, Yeo WS, Lim DY, Sivalingam V. Clinical Role of Aspirin in Mood Disorders: A Systematic Review. Brain Sci. 2019 Oct 29;9(11):296. doi: 10.3390/brainsci9110296.
citation: Marland S, Ellerton J, Andolfatto G, Strapazzon G, Thomassen O, Brandner B, Weatherall A, Paal P. Ketamine: use in anesthesia. CNS Neurosci Ther. 2013 Jun;19(6):381-9. doi: 10.1111/cns.12072. Epub 2013 Mar 22.
citation: Motov S, Rockoff B, Cohen V, Pushkar I, Likourezos A, McKay C, Soleyman-Zomalan E, Homel P, Terentiev V, Fromm C. Intravenous Subdissociative-Dose Ketamine Versus Morphine for Analgesia in the Emergency Department: A Randomized Controlled Trial. Ann Emerg Med. 2015 Sep;66(3):222-229.e1. doi: 10.1016/j.annemergmed.2015.03.004. Epub 2015 Mar 26.