Treatment Resistant DepressionPhase 4NCT05615948
Oral Aspirin + Ketamine as Adjunct to Oral Antidepressant Therapy for Depression
A Phase 4 study testing VTS-K in people with Treatment Resistant Depression and Major Depressive Disorder, run by Theresa Jacob, PhD, MPH at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 89 years
- Conditions the study is for
- Treatment Resistant Depression, Major Depressive Disorder, Analgesia
- What is being tested?
- VTS-K
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Dec 2022to 17 May 2024
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 89 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
:
- Conditions
- Treatment Resistant Depression, Major Depressive Disorder, Analgesia, Ketamine, Peripheral Nervous System Agents, Central Nervous System Depressants
- Being tested
- VTS-K
- Keywords
- Maimonides Medical Center, Psychiatry, Ketamine, Aspirin, Antipyretics, Peripheral Nervous System Agents, Sensory System Agents, Anesthetics, Dissociative, Excitatory Amino Acid Antagonists, Excitatory Amino Acid Agents, Cyclooxygenase Inhibitors, Oral Medications for depression
- Medical subject headings
- Depressive Disorder, Treatment-Resistant, Depressive Disorder, Major, Agnosia, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VTS-KDrug
Also called Ketamine + Aspirin
Proprietary oral formulation of 486mg aspirin and 80mg ketamine
| Study group | Role | What they receive |
|---|---|---|
| Intervention Group | Other | 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. Receives: Drug: VTS-K |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 7 Days
Secondary outcomes (4)
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.
Measured: 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.
:
Measured: 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.
Measured: 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. .
Measured: 4 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2022
- Study start6 Dec 2022
- Primary completion17 May 2024
- Study completion17 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Treatment Resistant DepressionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Theresa Jacob, PhD, MPH
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Theresa Jacob, PhD, MPH, Maimonides Medical Center
- Investigators
- Theresa Jacob, PhD, MPH, Study director, Maimonides Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05615948
- Sponsor's protocol ID
- 2022-01-22-MMC
- Status last verified
- Apr 2026
- First submitted
- 31 Oct 2022
- Last updated
- 21 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 31166571Wajs 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.
PubMed 32316080Ochs-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.
PubMed 31734084Ketterer 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.
PubMed 8730644Mendlewicz 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.
PubMed 16687994Ng 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.
PubMed 31671812Marland 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.
PubMed 23521979Motov 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.
PubMed 25817884
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05615948
- Acronym / sponsor ID
- 2022-01-22-MMC
- Conditions
- Treatment Resistant Depression, Major Depressive Disorder, Analgesia, Ketamine, Peripheral Nervous System Agents, Central Nervous System Depressants
- Keywords
- Maimonides Medical Center, Psychiatry, Ketamine, Aspirin, Antipyretics, Peripheral Nervous System Agents, Sensory System Agents, Anesthetics, Dissociative
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Theresa Jacob, PhD, MPHUniversity, hospital or other
- Study start
- 6 Dec 2022 (actual)
- Primary completion
- 17 May 2024 (actual)
- Study completion
- 17 May 2024 (actual)
- First posted
- 14 Nov 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
:
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intervention Group | Other | Drug: VTS-KAll 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. |
Who may qualify
- Ages
- 18 to 89 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VTS-KAlso: Ketamine + AspirinProprietary oral formulation of 486mg aspirin and 80mg ketamine | Drug | Intervention Group |
Primary outcome
Change in depressive symptoms on the Montgomery-Åsberg Depression Rating Scale (MADRS).
Time frame: 7 Days
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
4 secondary outcomes
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
Time frame: 4 Days
Clinician-Administered Dissociative States Scale (CADSS)
Time frame: 4 Days
Side Effect Rating Scale for Dissociative Anesthetics (SERSDA)
Time frame: 4 Days
Maximal sedative effects using Modified Observer's Assessment of Alertness and Sedation ( MOAA/S)
Time frame: 4 Days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2026.
- Background: PubMed 31166571Daly 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.
- Background: PubMed 32316080Wajs 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.
- Background: PubMed 31734084Ochs-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.
- Background: PubMed 8730644Ketterer 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.
- Background: PubMed 16687994Mendlewicz 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.
- Background: PubMed 31671812Ng 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.
- Background: PubMed 23521979Marland 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.
- Background: PubMed 25817884Motov 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.
Related trials for Treatment Resistant Depression
RecruitingPhase 4
Biomarker-Guided Antidepressant Selection
Depression - Major Depressive Disorder, Treatment-resistant Depression (TRD)
RecruitingPhase 2
ACP-211 Monotherapy for Major Depressive Disorder With Inadequate Antidepressant Response
Major Depressive Disorder (MDD), Depressive Disorder, Treatment-Resistant
Active, not recruiting
CET- REM (Correlating ECT Response to EEG Markers)
ECT, Treatment Resistant Depression
Active, not recruiting
rTMS to Target Neural Connectivity and Rumination in Treatment-Resistant Depression
Depression, Treatment Resistant
Recruiting
A Prospective, Multi-center, Randomized Controlled Blinded Trial Demonstrating the Safety and Effectiveness of VNS Therapy® System as Adjunctive Therapy Versus a No Stimulation Control in Subjects With Treatment-Resistant Depression
Treatment Resistant Depression
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Theresa Jacob, PhD, MPH study director
Maimonides Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing VTS-K in people with Treatment Resistant Depression and Major Depressive Disorder, run by Theresa Jacob, PhD, MPH at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in depressive symptoms on the Montgomery-Åsberg Depression Rating Scale (MADRS). (time frame: 7 Days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05615948, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Apr 2026.