DepressionPhase 2SADNCT03152409

Salicylic Augmentation in Depression

A Phase 2 study testing Aspirin 325mg in people with Depression and Depressive Disorder, run by Jessica Harder at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

The investigators are doing this research study to find out if using aspirin along with antidepressant treatment can lessen symptoms of depression. This study also aims to find out if some people improve more from taking aspirin than others. Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Depression, Depressive Disorder, Major Depressive Disorder
What is being tested?: Aspirin 325mg
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 32 participants
Where: 1 siteUnited States
Study dates: 15 Nov 2018to 16 Feb 2021
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Current diagnosis of major depressive disorder
Hamilton Depression Rating Scale (HDRS) score of >19
Stable treatment regimen (no medication changes or changes in psychotherapy treatment in past 8 weeks, and no participation in stepped treatments, such as completion of a course of cognitive behavioral therapy, during the trial)
Failed to remit with at least 1 antidepressant trial, or combination of 1 antidepressant and 1 augmentation agent
Women of childbearing age must agree to use an approved method of contraception for the duration of the study

Who cannot join

Active suicidal ideation
History of manic episodes or psychosis
Alcohol or substance use disorder up to one month prior to first testing session
Comorbid neurologic condition affecting the central nervous system
Comorbid autoimmune condition
Uncorrected thyroid disease or a current abnormal thyroid-stimulating hormone (TSH)

Show all 15Show fewer

Active or recent (within the past month) infection (such as otitis, pneumonia, urinary tract infection); temperature > 100.3 or white blood cell (WBC) count > 11 K/microL will be considered evidence of active infection even in the absence of other symptoms
History of GI bleed
History of stroke
History of a bleeding disorder
Platelet count < 150,000/mm3 on initial screening
On a blood-thinning agent or taking NSAIDs daily
Current use of oral steroids or other immunomodulating medications
Salicylate sensitivity
Pregnancy or breastfeeding

Trial locations and contacts

1 site in 1 country.

United States1 site

Brigham and Women's Hospital
Boston, Massachusetts, 02115

Other trials in United States

About this study

Aspirin is approved by the U.S. Food and Drug Administration (FDA) as an over-the-counter pain medication. But, aspirin is not approved by the FDA to make antidepressant treatment better.

This research study will compare aspirin to placebo.

Read the detailed description

This study is a randomized, double-blind, placebo-control trial. The primary aims of this study are:

Aim 1: To evaluate the clinical effect of aspirin augmentation on depression.

Aim 2: To assess the inflammatory profile of the blood of the aspirin augmentation responders compared with the non-responders.

Aim 3: To evaluate whether immune gene expression patterns are associated with antidepressant response to aspirin.

Aim 4: To collect samples for later, more detailed immunologic characterization.

Conditions: Depression, Depressive Disorder, Major Depressive Disorder, Treatment Resistant Depression
Being tested: Aspirin 325mg, Placebo Oral Tablet
Keywords: Aspirin, Treatment, Salicylic acid, anti-inflammatory
Medical subject headings: Depression, Depressive Disorder, Depressive Disorder, Major, Depressive Disorder, Treatment-Resistant

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Aspirin 325mgDrug
Also called Aspirin, Bayer, Salicylic acid
Participants will take intervention drug dose once a day in combination with their existing antidepressant treatment regimen.
Placebo Oral TabletDrug
Also called Placebo
Participants will take a placebo tablet of the same size, shape, and color as the aspirin tablet.

Study groups in NCT03152409
Study group	Role	What they receive
Aspirin augmentation to treatment	Active comparator	Participants who meet inclusion criteria for the study and are randomized to the active treatment arm will be given pills for the ensuing 8 weeks, consisting of a daily dose of aspirin 325 mg to be taken every evening before bed. Receives: Drug: Aspirin 325mg
Placebo augmentation to treatment	Placebo comparator	Participants randomized to the placebo arm will receive a placebo oral tablet of the same size, shape, and color as the aspirin tablet. Participants will be instructed to take their pills in the evening before bed. Receives: Drug: Placebo Oral Tablet

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Hamilton Depression Scale Score
Change in HDRS score in the treatment versus control groups.
Measured: 8 weeks

Secondary outcomes (2)

Response of Inflammatory Biomarkers
Response of inflammatory biomarkers in treatment responders versus treatment non-responders at 8 weeks.
Measured: 2 years
Biomarker Association With Antidepressant Response
Ability to observe the degree of biomarker association with antidepressant response.
Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

15 Nov 201816 Feb 2021

First posted15 May 2017
Study start15 Nov 2018
Primary completion16 Feb 2021
Study completion16 Feb 2021

Why it stopped: Inadequate resources to complete the study

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (8)Papers the sponsor has linked to this study.
Other trials for 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 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: Randomized control trial with about half of all participants receiving placebo.
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 32 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03152409
Sponsor's protocol ID: 2017P000525
Acronym: SAD
Status last verified: Jan 2024
First submitted: 13 Apr 2017
Last updated: 31 Jan 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Philip NS, Carpenter LL, Tyrka AR, Price LH. Pharmacologic approaches to treatment resistant depression: a re-examination for the modern era. Expert Opin Pharmacother. 2010 Apr;11(5):709-22. doi: 10.1517/14656561003614781.
PubMed 20151847
Berk M, Dean O, Drexhage H, McNeil JJ, Moylan S, O'Neil A, Davey CG, Sanna L, Maes M. Aspirin: a review of its neurobiological properties and therapeutic potential for mental illness. BMC Med. 2013 Mar 18;11:74. doi: 10.1186/1741-7015-11-74.
PubMed 23506529
Iyengar RL, Gandhi S, Aneja A, Thorpe K, Razzouk L, Greenberg J, Mosovich S, Farkouh ME. NSAIDs are associated with lower depression scores in patients with osteoarthritis. Am J Med. 2013 Nov;126(11):1017.e11-8. doi: 10.1016/j.amjmed.2013.02.037. Epub 2013 Aug 29.
PubMed 23993259
Muller N, Schwarz MJ, Dehning S, Douhe A, Cerovecki A, Goldstein-Muller B, Spellmann I, Hetzel G, Maino K, Kleindienst N, Moller HJ, Arolt V, Riedel M. The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: results of a double-blind, randomized, placebo controlled, add-on pilot study to reboxetine. Mol Psychiatry. 2006 Jul;11(7):680-4. doi: 10.1038/sj.mp.4001805. Epub 2006 Feb 21.
PubMed 16491133
Eyre HA, Air T, Proctor S, Rositano S, Baune BT. A critical review of the efficacy of non-steroidal anti-inflammatory drugs in depression. Prog Neuropsychopharmacol Biol Psychiatry. 2015 Mar 3;57:11-6. doi: 10.1016/j.pnpbp.2014.10.003. Epub 2014 Oct 16.
PubMed 25455584
Gallagher PJ, Castro V, Fava M, Weilburg JB, Murphy SN, Gainer VS, Churchill SE, Kohane IS, Iosifescu DV, Smoller JW, Perlis RH. Antidepressant response in patients with major depression exposed to NSAIDs: a pharmacovigilance study. Am J Psychiatry. 2012 Oct;169(10):1065-72. doi: 10.1176/appi.ajp.2012.11091325.
PubMed 23032386
Akhondzadeh S, Jafari S, Raisi F, Nasehi AA, Ghoreishi A, Salehi B, Mohebbi-Rasa S, Raznahan M, Kamalipour A. Clinical trial of adjunctive celecoxib treatment in patients with major depression: a double blind and placebo controlled trial. Depress Anxiety. 2009;26(7):607-11. doi: 10.1002/da.20589.
PubMed 19496103
Abbasi SH, Hosseini F, Modabbernia A, Ashrafi M, Akhondzadeh S. Effect of celecoxib add-on treatment on symptoms and serum IL-6 concentrations in patients with major depressive disorder: randomized double-blind placebo-controlled study. J Affect Disord. 2012 Dec 10;141(2-3):308-14. doi: 10.1016/j.jad.2012.03.033. Epub 2012 Apr 18.
PubMed 22516310

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Depression trials

Study at a glance

From the registry record, last updated by the sponsor on 31 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Salicylic Augmentation in Depression
ClinicalTrials.gov ID: NCT03152409
Acronym / sponsor ID: SAD / 2017P000525
Conditions: Depression, Depressive Disorder, Major Depressive Disorder, Treatment Resistant Depression
Keywords: Aspirin, Treatment, Salicylic acid, anti-inflammatory
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Inadequate resources to complete the study
Enrolment: 32 participants (actual)
Lead sponsor: Jessica HarderUniversity, hospital or other
Collaborators: Columbia University
Study start: 15 Nov 2018 (actual)
Primary completion: 16 Feb 2021 (actual)
Study completion: 16 Feb 2021 (actual)
First posted: 15 May 2017 (actual)
Results: Posted 31 Jan 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Aspirin is approved by the U.S. Food and Drug Administration (FDA) as an over-the-counter pain medication. But, aspirin is not approved by the FDA to make antidepressant treatment better.

This research study will compare aspirin to placebo.

Detailed description

This study is a randomized, double-blind, placebo-control trial. The primary aims of this study are:

Aim 1: To evaluate the clinical effect of aspirin augmentation on depression.

Aim 2: To assess the inflammatory profile of the blood of the aspirin augmentation responders compared with the non-responders.

Aim 3: To evaluate whether immune gene expression patterns are associated with antidepressant response to aspirin.

Aim 4: To collect samples for later, more detailed immunologic characterization.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 2
Model description: Randomized control trial with about half of all participants receiving placebo.

Arm	Type	Receives
Aspirin augmentation to treatment	Active comparator	Drug: Aspirin 325mgParticipants who meet inclusion criteria for the study and are randomized to the active treatment arm will be given pills for the ensuing 8 weeks, consisting of a daily dose of aspirin 325 mg to be taken every evening before bed.
Placebo augmentation to treatment	Placebo comparator	Drug: Placebo Oral TabletParticipants randomized to the placebo arm will receive a placebo oral tablet of the same size, shape, and color as the aspirin tablet. Participants will be instructed to take their pills in the evening before bed.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Current diagnosis of major depressive disorder
Hamilton Depression Rating Scale (HDRS) score of >19
Stable treatment regimen (no medication changes or changes in psychotherapy treatment in past 8 weeks, and no participation in stepped treatments, such as completion of a course of cognitive behavioral therapy, during the trial)
Failed to remit with at least 1 antidepressant trial, or combination of 1 antidepressant and 1 augmentation agent
Women of childbearing age must agree to use an approved method of contraception for the duration of the study

Key exclusion criteria (15 listed)

Active suicidal ideation
History of manic episodes or psychosis
Alcohol or substance use disorder up to one month prior to first testing session
Comorbid neurologic condition affecting the central nervous system
Comorbid autoimmune condition

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
Aspirin 325mgAlso: Aspirin, Bayer, Salicylic acidParticipants will take intervention drug dose once a day in combination with their existing antidepressant treatment regimen.	Drug	Aspirin augmentation to treatment
Placebo Oral TabletAlso: PlaceboParticipants will take a placebo tablet of the same size, shape, and color as the aspirin tablet.	Drug	Placebo augmentation to treatment

Primary outcome

Change in Hamilton Depression Scale Score
Time frame: 8 weeks
Change in HDRS score in the treatment versus control groups.

2 secondary outcomes

Response of Inflammatory Biomarkers
Time frame: 2 years
Biomarker Association With Antidepressant Response
Time frame: 2 years

Results and safety

Results posted to the registry on 31 Jan 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Aspirin Augmentation to Treatment	6	3
Placebo Augmentation to Treatment	5	3

Primary outcome: Change in Hamilton Depression Scale Score

Time frame: 8 weeks. Mean (Full Range). Unit: units on a scale

Measure	Aspirin Augmentation to Treatment n = 4	Placebo Augmentation to Treatment n = 3
Value	-9.75 (-16 to 5)	-11.67 (-21 to -7)

Population analysed: Analysis population consisted of study completers for whom HDRS scores from final study visit were available.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: 8 weeks. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Aspirin Augmentation to Treatment	3 of 6 (50%)	2 of 6 (33.3%)	0 of 6
Placebo Augmentation to Treatment	2 of 5 (40%)	3 of 5 (60%)	0 of 5

Limitations and caveats (from the sponsor): In Mar. 2020 study placed on prolonged pause due to the pandemic. Research activities resumed with limitations later that year. The last study participant was screened in Feb. 2021. However, personnel departure affected study activities, so study was again paused, with plans to resume once adequate personnel were hired. However no additional support was provided. In Dec. 2022, it was decided to terminate the study when it became clear that resources would be insufficient to complete the trial.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 20151847Philip NS, Carpenter LL, Tyrka AR, Price LH. Pharmacologic approaches to treatment resistant depression: a re-examination for the modern era. Expert Opin Pharmacother. 2010 Apr;11(5):709-22. doi: 10.1517/14656561003614781.
Background: PubMed 23506529Berk M, Dean O, Drexhage H, McNeil JJ, Moylan S, O'Neil A, Davey CG, Sanna L, Maes M. Aspirin: a review of its neurobiological properties and therapeutic potential for mental illness. BMC Med. 2013 Mar 18;11:74. doi: 10.1186/1741-7015-11-74.
Background: PubMed 23993259Iyengar RL, Gandhi S, Aneja A, Thorpe K, Razzouk L, Greenberg J, Mosovich S, Farkouh ME. NSAIDs are associated with lower depression scores in patients with osteoarthritis. Am J Med. 2013 Nov;126(11):1017.e11-8. doi: 10.1016/j.amjmed.2013.02.037. Epub 2013 Aug 29.
Background: PubMed 16491133Muller N, Schwarz MJ, Dehning S, Douhe A, Cerovecki A, Goldstein-Muller B, Spellmann I, Hetzel G, Maino K, Kleindienst N, Moller HJ, Arolt V, Riedel M. The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: results of a double-blind, randomized, placebo controlled, add-on pilot study to reboxetine. Mol Psychiatry. 2006 Jul;11(7):680-4. doi: 10.1038/sj.mp.4001805. Epub 2006 Feb 21.
Background: PubMed 25455584Eyre HA, Air T, Proctor S, Rositano S, Baune BT. A critical review of the efficacy of non-steroidal anti-inflammatory drugs in depression. Prog Neuropsychopharmacol Biol Psychiatry. 2015 Mar 3;57:11-6. doi: 10.1016/j.pnpbp.2014.10.003. Epub 2014 Oct 16.
Background: PubMed 23032386Gallagher PJ, Castro V, Fava M, Weilburg JB, Murphy SN, Gainer VS, Churchill SE, Kohane IS, Iosifescu DV, Smoller JW, Perlis RH. Antidepressant response in patients with major depression exposed to NSAIDs: a pharmacovigilance study. Am J Psychiatry. 2012 Oct;169(10):1065-72. doi: 10.1176/appi.ajp.2012.11091325.
Background: PubMed 19496103Akhondzadeh S, Jafari S, Raisi F, Nasehi AA, Ghoreishi A, Salehi B, Mohebbi-Rasa S, Raznahan M, Kamalipour A. Clinical trial of adjunctive celecoxib treatment in patients with major depression: a double blind and placebo controlled trial. Depress Anxiety. 2009;26(7):607-11. doi: 10.1002/da.20589.
Background: PubMed 22516310Abbasi SH, Hosseini F, Modabbernia A, Ashrafi M, Akhondzadeh S. Effect of celecoxib add-on treatment on symptoms and serum IL-6 concentrations in patients with major depressive disorder: randomized double-blind placebo-controlled study. J Affect Disord. 2012 Dec 10;141(2-3):308-14. doi: 10.1016/j.jad.2012.03.033. Epub 2012 Apr 18.
Individual participant dataSharing planned: No

Related trials for Depression

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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.

Jessica Harder, MD principal investigator

Brigham and Women's Hospital

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Aspirin 325mg in people with Depression and Depressive Disorder, run by Jessica Harder 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 5 inclusion and 15 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: stopped early, as of the sponsor's last update on 31 Jan 2024. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Jan 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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 Hamilton Depression Scale Score (time frame: 8 weeks). 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 NCT03152409, 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 31 Jan 2024.