Exercise + Ibuprofen for Bipolar Depression

Recruiting in Tulsa (>99 mi)

Overseen By Jonathan Savitz

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Laureate Institute for Brain Research, Inc.

Must not be taking: Immune-modulating, NSAIDs, Heart-modulating, others

Disqualifiers: Schizophrenia, Cardiac disease, Substance use, others

Compensation: Varies

Number of Visits: 4

20 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking certain medications like those with significant interactions with ibuprofen, immune-modulating medications, or regular NSAIDs more than 3 times a week.

What data supports the effectiveness of the treatment Exercise + Ibuprofen for Bipolar Depression?

Research suggests that exercise can help reduce symptoms of mood disorders like bipolar depression by improving mood stability and increasing cardiorespiratory fitness. Exercise has shown potential benefits in managing bipolar disorder by enhancing neurogenesis (growth of new brain cells) and reducing stress-related damage, which may improve both mental and physical health. ^{1 2 3 4 5}

Is exercise safe for people with bipolar disorder?

Research suggests that exercise can be beneficial for people with bipolar disorder, potentially improving both physical and mental health. However, the specific safety profile of exercise for this group is not well-documented, and individual experiences may vary. ^{1 2 3 6 7}

How does the treatment of exercise and ibuprofen differ from other treatments for bipolar depression?

This treatment combines high-intensity interval training (HIIT) with ibuprofen, which is unique because exercise can improve mood and brain function by increasing neurogenesis (growth of new brain cells) and reducing stress, while ibuprofen may help manage inflammation. Unlike standard drug treatments, this approach uses physical activity as a key component to potentially enhance both mental and physical health in bipolar depression. ^{1 2 3 4 6}

Eligibility Criteria

This trial is for adults aged 18-55 with bipolar depression, a BMI of 18.5-35, and who are stable on medication or deemed appropriate to participate. They must be able to undergo behavioral testing, MRI scans, and blood draws. Exclusions include severe substance abuse, complex psychiatric medication regimens, significant heart conditions or unstable medical issues, pregnancy or breastfeeding without contraception use, metal in the body that affects MRI safety, suicidal tendencies recently or certain medications like NSAIDs.

Inclusion Criteria

You have provided a signed and dated consent form.

My depression is severe, scoring over 11 on the QIDS.

I am currently experiencing a major depressive episode.

Exclusion Criteria

Clinically significant abnormality on EKG

You smoke a lot or smoke heavily according to the Fagerstrom scale.

I have or had heart disease, irregular heartbeats, or underwent a procedure to correct heart rhythm.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Experimental Sessions

Participants complete four experimental sessions, two with an exercise challenge and two with a resting control condition, receiving either ibuprofen or placebo.

4 sessions

4 visits (in-person)

Follow-up

Participants are monitored for neural and psychological effects post-intervention

2 hours post each session

Treatment Details

Interventions

• Acute Exercise
• Ibuprofen

Trial Overview The study tests if acute exercise can alleviate symptoms of bipolar depression by comparing four sessions: two involving exercise and two rest periods. Before these activities participants take either ibuprofen (800mg) or placebo to see if blocking inflammation affects the benefits of exercise on mood and brain function.

Participant Groups

Group I: Session 1 Experimental Treatment 2 Interventions

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

Group II: Session 3 Active Control 2 Interventions

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

Group III: Session 2 Active Control 2 Interventions

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

Group IV: Session 4 Placebo Group 2 Interventions

30 minutes rest (sitting in chair) and matching placebo

Who Is Running the Clinical Trial?

Laureate Institute for Brain Research, Inc.

Lead Sponsor

Trials

53

Recruited

5,400+

Findings from Research

Aerobic exercise, particularly high-intensity interval training (HIIT), may significantly help in managing symptoms of bipolar disorder (BD) by improving cardiorespiratory fitness (VO2max) and potentially stabilizing mood.

The review suggests that exercise can influence the pathophysiology of BD through mechanisms like monoaminergic action and neurotrophin release, indicating that physical activity could be a valuable adjunct to traditional treatments for BD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise is medicine: a new perspective for health promotion in bipolar disorder. Sá Filho, AS., Cheniaux, E., de Paula, CC., et al.[2021]

This study will evaluate the efficacy of exercise as a treatment for bipolar disorder in 100 patients aged 20-65, comparing an exercise intervention with a placebo stretching intervention over a 6-week period.

The research aims to provide comprehensive evidence on the effectiveness of exercise by assessing various clinical, biological, and genetic markers, potentially establishing exercise as a beneficial treatment for bipolar depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Exercise on Functional Recovery in Patients with Bipolar Depression: A Study Protocol for a Randomized Controlled Trial. Hamada, F., Hori, H., Iida, H., et al.[2023]

Structured individualized physical exercise can significantly alleviate affective and cognitive difficulties in individuals with bipolar disorder (BD), suggesting it may improve overall mental health.

Exercise is proposed to positively influence neurobiological systems related to metabolism, inflammation, and cellular health, potentially leading to better psychiatric and physical outcomes for those with BD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise and bipolar disorder: a review of neurobiological mediators. Alsuwaidan, MT., Kucyi, A., Law, CW., et al.[2021]

Patients with bipolar disorder often experience suboptimal outcomes with medication alone, and adding exercise could significantly enhance both short-term and long-term results.

Exercise may improve mood and functioning in bipolar disorder by increasing brain-derived neurotrophic factor (BDNF), which promotes neurogenesis and reduces stress on the body, suggesting a need for further clinical trials to explore this adjunct treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise treatment for bipolar disorder: potential mechanisms of action mediated through increased neurogenesis and decreased allostatic load. Sylvia, LG., Ametrano, RM., Nierenberg, AA.[2010]

Adolescents with bipolar disorder (BD) showed significantly lower exercise tolerance and cardiorespiratory fitness compared to healthy controls, indicating a potential barrier to engaging in physical activity.

While exercise preference did not differ significantly between groups, lower exercise preference in youth with BD was linked to lower fitness levels and higher perceived exertion, suggesting that improving fitness may enhance their willingness to exercise.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise preference and tolerance in youth with bipolar disorder. Shickh, R., Mio, M., Khoubaeva, D., et al.[2023]

A study involving 25 individuals with Bipolar Disorder highlighted that exercise can play a significant role in mood regulation, but it also has potential risks, indicating it can be a 'double-edged sword' for those with the condition.

Participants noted that exercise helps bring structure to their lives, suggesting that incorporating physical activity could be beneficial in managing Bipolar Disorder, but more research is needed to understand the nuances of this relationship.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

'It's a double edged sword': a qualitative analysis of the experiences of exercise amongst people with Bipolar Disorder. Wright, K., Armstrong, T., Taylor, A., et al.[2018]

Participation in a long-distance ski race was linked to a significantly lower risk of being diagnosed with bipolar disorder, with a hazard ratio of 0.48 over a follow-up period of up to 21 years, based on a study of nearly 200,000 skiers and matched non-skiers.

While a physically active lifestyle generally reduces the risk of bipolar disorder, higher performance in women (indicated by faster race finishing times) was associated with an increased risk, suggesting that exercise intensity may have different effects based on sex.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A physically active lifestyle is associated with lower long-term incidence of bipolar disorder in a population-based, large-scale study. Svensson, M., Erhardt, S., Hållmarker, U., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Exercise is medicine: a new perspective for health promotion in bipolar disorder. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Effects of Exercise on Functional Recovery in Patients with Bipolar Depression: A Study Protocol for a Randomized Controlled Trial. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Exercise and bipolar disorder: a review of neurobiological mediators. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Exercise treatment for bipolar disorder: potential mechanisms of action mediated through increased neurogenesis and decreased allostatic load. [2010]

5. England pubmed.ncbi.nlm.nih.gov

Exercise preference and tolerance in youth with bipolar disorder. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

'It's a double edged sword': a qualitative analysis of the experiences of exercise amongst people with Bipolar Disorder. [2018]

7. Germany pubmed.ncbi.nlm.nih.gov

A physically active lifestyle is associated with lower long-term incidence of bipolar disorder in a population-based, large-scale study. [2022]