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

Major Depressive Disorder Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05615948
• Other study ID #: 2022-01-22-MMC
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: December 6, 2022
• Est. completion date: October 31, 2024

Study information

• Verified date: April 2024
• Source: Maimonides Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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. :

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 20
• Est. completion date: October 31, 2024
• Est. primary completion date: October 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 89 Years

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• VTS-K
Proprietary oral formulation of 486mg aspirin and 80mg ketamine

Locations

Country	Name	City	State
United States	Maimonides Medical Center	Brooklyn	New York

Sponsors (1)

Lead Sponsor	Collaborator
Maimonides Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (8)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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