NCT02507219

Brief Summary

The aim of this project is to determine whether the acute oral administration of Ibuprofen changes the activation pattern in the amygdala and other brain structures during functional magnetic resonance imaging. The investigators use a double-blind, randomized, repeated-measures design. Each of the 20 healthy control subjects will be tested three times and receive placebo, 200 mg or 600 mg dose of ibuprofen p.o. The study will consist of 4 sessions: a baseline screening session and 3 testing sessions scheduled 1-2 weeks apart. Each of these individuals will undergo a multi-level assessment based on the RDoC approach that consists of (a) a standardized diagnostic assessment, (b) self-report questionnaires assessing the positive and negative valence domains as well as interoception, (c) behavioral tasks assessing reward-related processing, avoidance, and aversive processing, cognition, and interoception; (d) physiological measurements consisting of facial emotion expression monitoring, heart rate and respiration, (e) functional magnetic resonance imaging focusing on reward-related processing, fear conditioning and extinction, cognitive inhibition, and interoceptive processing, and (f) biomarker assessments.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
24

participants targeted

Target at below P25 for phase_2 major-depressive-disorder

Timeline
Completed

Started Jul 2015

Shorter than P25 for phase_2 major-depressive-disorder

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2015

Completed
21 days until next milestone

First Submitted

Initial submission to the registry

July 22, 2015

Completed
1 day until next milestone

First Posted

Study publicly available on registry

July 23, 2015

Completed
2 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2015

Completed
2.4 years until next milestone

Results Posted

Study results publicly available

February 23, 2018

Completed
Last Updated

February 23, 2018

Status Verified

January 1, 2018

Enrollment Period

3 months

First QC Date

July 22, 2015

Results QC Date

May 5, 2017

Last Update Submit

January 26, 2018

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (1)

  • Dose-dependent Differences in the BOLD Response to fMRI Tasks in the Amygdala

    Change in amygdala activation following administration of placebo, 200mg of ibuprofen or 600mg of ibuprofen

    3-6 weeks

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Subjects will receive one dose of placebo (sugar pill) at one of the three testing sessions . Placebo capsules will be produced in the same manner as the ibuprofen by a local compounding pharmacy in Tulsa, OK.

Drug: Ibuprofen

Ibuprofen, 200mg

ACTIVE COMPARATOR

Subjects will receive one oral dose of 200mg at one of the three testing sessions. Ibuprofen capsules will be produced by a local compounding pharmacy in Tulsa, OK.

Drug: Ibuprofen

Ibuprofen, 600mg

ACTIVE COMPARATOR

Subjects will receive one oral dose of 600mg at one of the three testing sessions. Ibuprofen capsules will be produced by a local compounding pharmacy in Tulsa, OK.

Drug: Ibuprofen

Interventions

IbuprofenDRUG

On the day of sessions 2-4, subjects will receive either placebo, 200 mg of ibuprofen or 600 mg of ibuprofen after signing the consent form for this study in a randomized, double-blind, counter balanced order. Each study session will occur 1-2 weeks following the previous session. Ibuprofen will be capsuled, and identical placebo capsules will be produced.

Also known as: Placebo
Ibuprofen, 200mgIbuprofen, 600mgPlacebo

Eligibility Criteria

Age18 Years - 55 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Male, or female
  • Between the ages of 18-50.
  • In good general health

You may not qualify if:

  • Subjects who report a history of any mental health disorder such as dysthymia, simple phobia, major depression, obsessive compulsive disorder or panic disorder as a primary diagnosis currently or within 6 months prior to the screening visit.
  • Subjects with a history of schizophrenia, schizoaffective disorder, or a bipolar disorder.
  • Subjects who report DSM-V criteria for substance use disorder (alcohol or drugs) currently or within 6 months prior to screening
  • Subjects who have a positive urine illicit drug screen.
  • Subjects that regularly (more than 15 days for past 30 days) use NSAIDS and have not used NSAIDS in the previous 5 days.
  • Subjects with a history of clinically significant hepatic cardiac, renal, neurologic, cerebrovascular, metabolic or pulmonary disease, gastric disease.
  • Subjects who have taken psychotropic drugs or antidepressants (including monoamine oxidase inhibitors, MAOI's) within the last year
  • Subjects with a history of seizure disorders (except for febrile seizures in childhood).
  • Subjects who, in the investigator's judgment pose a current, serious suicidal or homicidal risk or have made a suicide attempt within the past 6 months.
  • Women who have a positive serum HCG pregnancy test at screen visit or who are lactating or planning to become pregnant within the next 18 weeks following the screen visit.
  • Women who are currently menstruating.
  • The subject suffers from claustrophobia, or phobia for injections or blood.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Laureate Institute for Brain Research

Tulsa, Oklahoma, 74136, United States

Location

Related Publications (9)

  • Delaney JA, Biggs ML, Kronmal RA, Psaty BM. Demographic, medical, and behavioral characteristics associated with over the counter non-steroidal anti-inflammatory drug use in a population-based cohort: results from the Multi-Ethnic Study of Atherosclerosis. Pharmacoepidemiol Drug Saf. 2011 Jan;20(1):83-9. doi: 10.1002/pds.2065. Epub 2010 Nov 11.

    PMID: 21182156BACKGROUND

  • Hersh EV, Pinto A, Moore PA. Adverse drug interactions involving common prescription and over-the-counter analgesic agents. Clin Ther. 2007;29 Suppl:2477-97. doi: 10.1016/j.clinthera.2007.12.003.

    PMID: 18164916BACKGROUND

  • Andrade C. Antidepressant augmentation with anti-inflammatory agents. J Clin Psychiatry. 2014 Sep;75(9):975-7. doi: 10.4088/JCP.14f09432.

    PMID: 25295422BACKGROUND

  • Saleh LA, Hamza M, El Gayar NH, Abd El-Samad AA, Nasr EA, Masoud SI. Ibuprofen suppresses depressive like behavior induced by BCG inoculation in mice: role of nitric oxide and prostaglandin. Pharmacol Biochem Behav. 2014 Oct;125:29-39. doi: 10.1016/j.pbb.2014.07.013. Epub 2014 Aug 4.

    PMID: 25101545BACKGROUND

  • 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: 23993259BACKGROUND

  • Fields C, Drye L, Vaidya V, Lyketsos C; ADAPT Research Group. Celecoxib or naproxen treatment does not benefit depressive symptoms in persons age 70 and older: findings from a randomized controlled trial. Am J Geriatr Psychiatry. 2012 Jun;20(6):505-13. doi: 10.1097/JGP.0b013e318227f4da.

    PMID: 21775876BACKGROUND

  • Warner-Schmidt JL, Vanover KE, Chen EY, Marshall JJ, Greengard P. Antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) are attenuated by antiinflammatory drugs in mice and humans. Proc Natl Acad Sci U S A. 2011 May 31;108(22):9262-7. doi: 10.1073/pnas.1104836108. Epub 2011 Apr 25.

    PMID: 21518864BACKGROUND

  • Delli Pizzi S, Mantini D, Ferretti A, Caulo M, Salerio I, Romani GL, Del Gratta C, Tartaro A. Pharmacological functional MRI assessment of the effect of ibuprofen-arginine in painful conditions. Int J Immunopathol Pharmacol. 2010 Jul-Sep;23(3):927-35. doi: 10.1177/039463201002300329.

    PMID: 20943065BACKGROUND

  • Le TT, Kuplicki R, Yeh HW, Aupperle RL, Khalsa SS, Simmons WK, Paulus MP. Effect of Ibuprofen on BrainAGE: A Randomized, Placebo-Controlled, Dose-Response Exploratory Study. Biol Psychiatry Cogn Neurosci Neuroimaging. 2018 Oct;3(10):836-843. doi: 10.1016/j.bpsc.2018.05.002. Epub 2018 Jun 23.

    PMID: 29941380DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Ibuprofen

Condition Hierarchy (Ancestors)

Depressive DisorderMood DisordersMental Disorders

Intervention Hierarchy (Ancestors)

PhenylpropionatesAcids, CarbocyclicCarboxylic AcidsOrganic Chemicals

Results Point of Contact

Title
Dr. Martin Paulus
Organization
Laureate Institute for Brain Research
mpaulus@laureateinstitute.org
918-502-5120

Study Officials

  • Martin P Paulus, M.D.

    Laureate Institute for Brain Research

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
BASIC SCIENCE
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 22, 2015

First Posted

July 23, 2015

Study Start

July 1, 2015

Primary Completion

October 1, 2015

Study Completion

October 1, 2015

Last Updated

February 23, 2018

Results First Posted

February 23, 2018

Record last verified: 2018-01

Locations

US(1)