Effects of Acute Exercise and Ibuprofen on Symptoms, Immunity, and Neural Circuits in Bipolar Depression

NCT06088732 | Recruiting Phase 1

• 1 other identifier: 2023-001
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This is a 2x2, within-subjects, cross-over trial to test the anti-depressant effects of acute exercise in 20 participants with bipolar depression. Participants will complete four experimental sessions, two with an exercise challenge and two with a resting control condition in a counterbalanced order. Participants will receive either 800mg of ibuprofen or placebo before exercise or rest in order to test whether blocking the inflammatory response to exercise interferes with the neural and psychological effects of exercise.

Conditions

Bipolar Depression

Outcome Measures

Primary Outcomes (2)

• Inflammation

  Serum concentrations of interleukin 6 (IL-6)

  Difference between IL-6 at baseline and two hours post intervention

• Neural Response to Reward Anticipation

  Percent Signal Change in Ventral Striatum During Monetary Incentive Delay

  One hour post intervention

Secondary Outcomes (5)

• Neural Response to Reward Receipt

  One hour post intervention

• Brain Volume

  One hour post intervention

• Inflammation

  Difference between TNF at baseline and two hours post intervention

• Inflammation

  Difference between IL-10 at baseline and two hours post intervention

• Anhedonia

  Difference between SHAPS scores at baseline and two hours post intervention

Study Arms (4)

Session 1

EXPERIMENTAL

Exercise (30 min on bicycle ergometer at 60% peak power output) and a single oral dose 800mg of ibuprofen

Other: Exercise Session; Drug: Ibuprofen 800 mg

Session 2

ACTIVE COMPARATOR

Exercise (30 min on bicycle ergometer at 60% peak power output) and matching placebo

Other: Exercise Session; Drug: Placebo

Session 3

ACTIVE COMPARATOR

30 minutes rest (sitting in chair) and a single oral dose 800mg of ibuprofen

Drug: Ibuprofen 800 mg; Other: Rest

Session 4

PLACEBO COMPARATOR

30 minutes rest (sitting in chair) and matching placebo

Other: Rest; Drug: Placebo

Interventions

Exercise Session OTHER

30 min cycling on bicycle ergometer at 60% peak power output

Session 1; Session 2

Ibuprofen 800 mg DRUG

A single oral dose of Ibuprofen

Session 1; Session 3

Rest OTHER

Resting for 30 min in chair

Session 3; Session 4

Placebo DRUG

Matched placebo

Session 2; Session 4

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Provision of signed and dated informed consent form
• Has an established residence and phone
• Agrees to and is eligible for behavioral testing, magnetic resonance imaging, and blood draws.
• Stated willingness to comply with all study procedures and lifestyle considerations (see Section 5.3, Lifestyle Considerations) and availability for the duration of the study
• Males and females; Age 18-55 years
• DSM-V diagnosis of bipolar disorder
• Has a current major depressive episode
• Depression at enrollment of sufficient severity to score \> 11 on the QIDS
• Be stably medicated for at least 4 weeks (a non-medicated subject may be included in the study if judged to be appropriate in the medical/psychiatric opinion of the investigator)
• BMI between 18.5 and 35

You may not qualify if:

• Diagnosis of any other major psychiatric disorder such as schizoaffective disorder, schizophrenia, or current psychotic depression
• A history of bipolar disorder with rapid cycling
• Concurrent manic symptoms of sufficient severity to pose a substantial risk of the development of a manic episode (\>19 on the YMRS)
• Current drug or alcohol or substance use disorder moderate or severe, except nicotine (within 6 months for severe use disorder; 2 months for moderate use disorder)
• Volunteers currently receiving more than 4 mood-relevant psychotropic medications in a daily regimen (since this may signify a more brittle or complex clinical state)
• Taking any of the following medications: medications with significant interactions with ibuprofen; immune-modulating medications (e.g. oral steroids); regular use of NSAIDs (\> 3 times per week)
• Current or prior cardiac disease, cardiac arrhythmia (e.g. supraventricular tachycardia, atrial fibrillation, ventricular fibrillation), or history of cardiac ablation therapy
• Unstable medical condition, including significant respiratory disease (e.g., asthma, reactive airway disease (i.e., exercise induced asthma), or chronic obstructive pulmonary disease (COPD)), liver disease, hypothyroidism (i.e., condition not adequately stabilized for 3 months), or other conditions likely to require hospitalization or with a life expectancy of \< 6 months (e.g., cancer).
• History of claustrophobia that would prevent participation in imaging scans
• Actively suicidal, as defined by expressive ideation with a plan and intent for suicide or developing suicidal ideation that requires immediate medical or treatment intervention or a suicide attempt within the previous six months
• Participants who endorse a history of moderate to severe traumatic brain injury (\>30 min. loss of consciousness or \>24 hours posttraumatic amnesia) or other neurocognitive disorder with evidence of neurological deficits
• Inadequate understanding of English
• Currently pregnant or breast-feeding; fecund women not using adequate contraceptive methods; plan to become pregnant within 12 months
• Metal in the body (e.g. history of working as a sheet metal worker) or pacemaker which is a contra-indication to magnetic resonance imaging
• Has epilepsy, a neuromuscular disorder, or tardive dyskinesia

Sponsors & Collaborators

• Laureate Institute for Brain Research, Inc.: lead

Study Sites (1)

Laureate Institute for Brain Research

Tulsa, Oklahoma, 74136, United States

RECRUITING

MeSH Terms

Conditions

Bipolar Disorder

Interventions

Ibuprofen; RE1-silencing transcription factor

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals

Central Study Contacts

Jonathan Savitz

CONTACT

9185025104; jsavitz@laureateinstitute.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2023
• First Posted: October 18, 2023
• Study Start: March 12, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 23, 2025

Record last verified: 2025-05

Locations

US (1)