Salicylic Augmentation in Depression

NCT03152409 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: 2017P000525
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief 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. The investigators also want to see if it is possible to predict which participants will do better based on a blood test. 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.

Conditions

Depression; Depressive Disorder; Major Depressive Disorder; Treatment Resistant Depression

Keywords

Aspirin; Treatment; Salicylic acid; anti-inflammatory

Outcome Measures

Primary Outcomes (1)

• Change in Hamilton Depression Scale Score

  Change in HDRS score in the treatment versus control groups.

  8 weeks

Secondary Outcomes (2)

• Response of Inflammatory Biomarkers

  2 years

• Biomarker Association With Antidepressant Response

  2 years

Study Arms (2)

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.

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.

Drug: Placebo Oral Tablet

Interventions

Aspirin 325mg DRUG

Participants will take intervention drug dose once a day in combination with their existing antidepressant treatment regimen.

Also known as: Aspirin, Bayer, Salicylic acid

Aspirin augmentation to treatment

Placebo Oral Tablet DRUG

Participants will take a placebo tablet of the same size, shape, and color as the aspirin tablet.

Also known as: Placebo

Placebo augmentation to treatment

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• Jessica Harder: lead
• Columbia University: collaborator

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Related Publications (8)

• 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.

  PMID: 20151847 BACKGROUND

• 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.

  PMID: 23506529 BACKGROUND

• 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.

  PMID: 23993259 BACKGROUND

• 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.

  PMID: 16491133 BACKGROUND

• 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.

  PMID: 25455584 BACKGROUND

• 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.

  PMID: 23032386 BACKGROUND

• 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.

  PMID: 19496103 BACKGROUND

• 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.

  PMID: 22516310 BACKGROUND

MeSH Terms

Conditions

Depression; Depressive Disorder; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant

Interventions

Aspirin; Salicylic Acid

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Hydroxy Acids

Limitations and Caveats

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.

Results Point of Contact

• Title: Dr. Jessica Harder
• Organization: Brigham and Women's Hospital

jaharder@bwh.harvard.edu

6177326753

Study Officials

• Jessica Harder, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Study team will be blinded to participant condition. Pharmacy will be responsible for providing study drug versus identical placebo to participants.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principle Investigator

Model Details: Randomized control trial with about half of all participants receiving placebo.

Study Record Dates

• First Submitted: April 13, 2017
• First Posted: May 15, 2017
• Study Start: November 15, 2018
• Primary Completion: February 16, 2021
• Study Completion: February 16, 2021
• Last Updated: January 31, 2024
• Results First Posted: January 31, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)