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

Bipolar Depression Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06088732
• Other study ID #: 2023-001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 12, 2024
• Est. completion date: December 31, 2026

Study information

• Verified date: March 2024
• Source: Laureate Institute for Brain Research, Inc.
• Contact: Jonathan Savitz
• Phone: 9185025104
• Email: jsavitz[@]laureateinstitute.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Bipolar Depression
• Bipolar Disorder
• Depression
• Depressive Disorder

Intervention

Other:
• Exercise Session
30 min cycling on bicycle ergometer at 60% peak power output

Drug:
• Ibuprofen 800 mg
A single oral dose of Ibuprofen

Other:
• Rest
Resting for 30 min in chair

Drug:
• Placebo
Matched placebo

Locations

Country	Name	City	State
United States	Laureate Institute for Brain Research	Tulsa	Oklahoma

Sponsors (1)

Lead Sponsor	Collaborator
Laureate Institute for Brain Research, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Inflammation	Serum concentrations of interleukin 6 (IL-6)	Difference between IL-6 at baseline and two hours post intervention
Primary	Neural Response to Reward Anticipation	Percent Signal Change in Ventral Striatum During Monetary Incentive Delay	One hour post intervention
Secondary	Neural Response to Reward Receipt	Percent Signal Change in Ventral Striatum During Monetary Incentive Delay (MID) task	One hour post intervention
Secondary	Brain Volume	Gray Matter Volume of the Hippocampus	One hour post intervention
Secondary	Inflammation	Serum concentrations of tumor necrosis factor (TNF)	Difference between TNF at baseline and two hours post intervention
Secondary	Inflammation	Serum concentrations of interleukin 10 (IL-10)	Difference between IL-10 at baseline and two hours post intervention
Secondary	Anhedonia	Score on the Snaith-Hamilton Pleasure Scale (SHAPS). Higher scores indicate greater anhedonia. Score range from 0-14.	Difference between SHAPS scores at baseline and two hours post intervention