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

NCT ID: NCT06088732

Last Updated: 2025-05-23

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-12
• Study Completion Date: 2026-12-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

Session 1

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

Group Type: EXPERIMENTAL

Exercise Session

Intervention Type: OTHER

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

Ibuprofen 800 mg

Intervention Type: DRUG

A single oral dose of Ibuprofen

Session 2

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

Group Type: ACTIVE_COMPARATOR

Exercise Session

Intervention Type: OTHER

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

Placebo

Intervention Type: DRUG

Matched placebo

Session 3

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

Group Type: ACTIVE_COMPARATOR

Ibuprofen 800 mg

Intervention Type: DRUG

A single oral dose of Ibuprofen

Rest

Intervention Type: OTHER

Resting for 30 min in chair

Session 4

30 minutes rest (sitting in chair) and matching placebo

Group Type: PLACEBO_COMPARATOR

Rest

Intervention Type: OTHER

Resting for 30 min in chair

Placebo

Intervention Type: DRUG

Matched placebo

Interventions

Exercise Session

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

Intervention Type: OTHER

Ibuprofen 800 mg

A single oral dose of Ibuprofen

Intervention Type: DRUG

Rest

Resting for 30 min in chair

Intervention Type: OTHER

Placebo

Matched placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Provision of signed and dated informed consent form

2. Has an established residence and phone

3. Agrees to and is eligible for behavioral testing, magnetic resonance imaging, and blood draws.

4. 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

5. Males and females; Age 18-55 years

6. DSM-V diagnosis of bipolar disorder

7. Has a current major depressive episode

8. Depression at enrollment of sufficient severity to score > 11 on the QIDS

9. 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)

10. BMI between 18.5 and 35

Exclusion Criteria

1. Diagnosis of any other major psychiatric disorder such as schizoaffective disorder, schizophrenia, or current psychotic depression

2. A history of bipolar disorder with rapid cycling

3. Concurrent manic symptoms of sufficient severity to pose a substantial risk of the development of a manic episode (>19 on the YMRS)

4. 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)

5. 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)

6. 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)

7. Current or prior cardiac disease, cardiac arrhythmia (e.g. supraventricular tachycardia, atrial fibrillation, ventricular fibrillation), or history of cardiac ablation therapy

8. 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).

9. History of claustrophobia that would prevent participation in imaging scans

10. 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

11. 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

12. Inadequate understanding of English

13. Currently pregnant or breast-feeding; fecund women not using adequate contraceptive methods; plan to become pregnant within 12 months

14. 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

15. Has epilepsy, a neuromuscular disorder, or tardive dyskinesia

16. Has a chronic infectious illness

17. Requires immediate hospitalization for psychiatric disorder

18. Requires medications for a general medical condition that contraindicate any study medication

19. Receiving or have received during the index episode vagus nerve stimulation, electroconvulsive therapy, transcranial magnetic stimulation, or other somatic treatments

20. Allergy to, or other medical contraindication to ibuprofen (e.g. stomach ulcers)

21. Symptoms of myalgic encephalomyelitis/chronic fatigue syndrome or "long-COVID".

22. Current use of medications or dietary supplements for weight or appetite control, whether prescribed or not

23. Ulcerative colitis, Crohn's disease or other autoimmune disorder (except treated hypothyroidism)

24. Activity restrictions that limit the subject's ability to engage in intense physical activity

25. Use of beta-blockers, calcium channel inhibitors, or other heart-modulating medications (e.g., amiodarone)

26. Clinically significant abnormality on EKG

27. Hypertension, hepatitis, renal dysfunction, and/or anemia of sufficient severity to pose a risk to the participant

28. Moderate or heavy smoker based on Fagerstrom

29. Resting heart rate >100 beats per minute, systolic blood pressure > 160 mmHg, diastolic blood pressure > 100 mmHg

30. Clinically significant screening laboratory abnormalities not covered above

31. Any reason not listed herein that would make participation in the study hazardous

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Laureate Institute for Brain Research, Inc.

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Laureate Institute for Brain Research

Tulsa, Oklahoma, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Jonathan Savitz

Role: CONTACT

jsavitz@laureateinstitute.org

9185025104

Facility Contacts

Jonathan Savitz, PhD

Role: primary

jsavitz@laureateinstitute.org

918-502-5104

Other Identifiers

2023-001

Identifier Type: -

Identifier Source: org_study_id