Bipolar Depression
Conditions
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.
Interventions
OTHERExercise Session
30 min cycling on bicycle ergometer at 60% peak power output
DRUGIbuprofen 800 mg
A single oral dose of Ibuprofen
OTHERRest
Resting for 30 min in chair
DRUGPlacebo
Matched placebo
Sponsors
Laureate Institute for Brain Research, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Inflammation | Difference between IL-6 at baseline and two hours post intervention | Serum concentrations of interleukin 6 (IL-6) |
| Neural Response to Reward Anticipation | One hour post intervention | Percent Signal Change in Ventral Striatum During Monetary Incentive Delay |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Neural Response to Reward Receipt | One hour post intervention | Percent Signal Change in Ventral Striatum During Monetary Incentive Delay (MID) task |
| Brain Volume | One hour post intervention | Gray Matter Volume of the Hippocampus |
| Inflammation | Difference between TNF at baseline and two hours post intervention | Serum concentrations of tumor necrosis factor (TNF) |
| Anhedonia | Difference between SHAPS scores at baseline and two hours post intervention | Score on the Snaith-Hamilton Pleasure Scale (SHAPS). Higher scores indicate greater anhedonia. Score range from 0-14. |
Countries
United States
Contacts
Primary ContactJonathan Savitz
Outcome results
None listed