Effects of Low Dose Aspirin in Bipolar Disorder (The A-Bipolar RCT)

Study Overview
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Brief Summary
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Despite currently available treatment, a large proportion of patients with bipolar disorder (BD) suffer from affective symptoms, impaired psychosocial and cognitive function. Inflammation seems to be involved in the pathogenesis of BD and preliminary data suggest that low-dose Aspirin may have beneficial effects. The objective of this RCT is to investigate whether add on of low dose aspirin versus placebo add on to standard drug treatment improves mood stabilisation and other critical patient outcomes in patients with BD and whether its principal effects are antimanic, antidepressant or prophylactic against relapse. randomized double-blinded placebo-controlled trial will investigate whether augmentation with low dose Aspirin to standard drug treatment improve mood stabilization.

Detailed Description
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BD is increasingly conceived as a multisystem disorder with pathophysiologic abnormalities involving inflammation, oxidative stress imbalance, neurotrophic deficiencies and telomere shortening. Specifically, inflammation has been confirmed to be involved in the pathogenesis of BD. Emerging yet compelling data converge to suggest that aspirin may protect against the onset and deterioration in BD. Nevertheless, a pragmatic large scale RCT is needed to for a conclusive risk-benefit analysis of aspirin and to clarify its therapeutic role at the different clinical stages of BD.The investigators propose to include smartphone-based self-assessment of mood as the primary outcome measure in the RCT. Thus, during the last ten years, the investigators have developed and tested a unique smartphone-based system, the Monsenso system, for monitoring, diagnosing and treating BD. The trial is designed as a two arm, parallel randomized trial with randomisation 1:1 to add on of low dose aspirin (Hjertemagnyl 150 mg/day) versus add-on of placebo to current treatment and with stratification according to age (< 30 years) and gender. The trial is planned and will be conducted in concordance with the CONSORT 2010 Explanation and Elaboration: updated guidelines for reporting parallel group randomised trials. Patients will be included from The Copenhagen Affective Disorder Clinic, which is a mood disorder clinic providing treatment service for patients with newly diagnosed/first episode BD from the entire Capital Region of Denmark covering a catchment area of 1.6 million people and all psychiatric centres in the region. The Clinic receives more than 300 patients with newly diagnosed BD each year. Hypotheses: Primary: Add on low dose aspirin versus placebo to standard drug treatment improves mood stabilisation. Secondary: Effects on mood stabilisation is higher in patients with increased inflammatory marker levels at inclusion Tertiary: Low dose aspirin improves cognition.

Official Title
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Effects of Low Dose Aspirin in Bipolar Disorder (The A-Bipolar RCT)

Conditions
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Bipolar Disorder

Intervention / Treatment
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* Drug: acetylsalicylic acid
* Drug: Calcium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Bipolar disorder (type 1 or 2), with diagnoses confirmed by SCAN interview. Age 18-65 years Speaks and writes Danish at a level equal to mother tongue Habile (i.e. able to give informed consent) Exclusion Criteria: Chronic kidney disease with GFR 0-10 ml/min Severe cardiac insufficiency (NYHA IIIb-IV) History of gastric ulcers, gastro-intestinal bleeding or other pathological bleeding tendency (thrombocytopenia, hemophilia, vitamin K deficiency) Asthma or other allergic symptoms developed after intake of salicylates, paracetamol or other NSAID or any of the excipients Patients already on aspirin or other NSAID, anticoagulants or SSRIs. For fertile females: Reluctance to use effective contraception during enrollment, including a safety period of one week following last medication day/trial completion Pregnancy; pregnancy ruled out by HCG test before enrollment Breastfeeding Planned major surgery during trial period. If a subject has scheduled major surgery (i.e. with bleeding risk), enrollment will be postponed until this is completed

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double-blinded randomized placebo-controlled trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>125 BD participants will receive placebo. Patients, clinicians and researchers will be blinded for the intervention | Drug: Calcium<br>* Oral tablet: calcium, 1 tablet/day<br>|
| Active Comparator: Active<br>125 BD participants will receive active treatment. Patients, clinicians and researchers will be blinded for the intervention | Drug: acetylsalicylic acid<br>* Oral tablet: acetylsalicylic acid,150 mg, 1 tablet/day<br>* Other names: Aspirin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Daily self-reported mood instability | Daily self-reported mood instability collected via the Monsenso system | 6 months (12 months for a subgroup of participants) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Depressive symptoms | Depressive symptoms assessed by the Hamilton Depression Rating Scale-6 items (min. value = 0; max. value = 22, with higher values reflecting more depressive symptoms) | 6 months (12 months for a subgroup of participants) | 
| Manic symptoms | Manic symptoms assessed by the Young Mania Rating Scale (min. value = 0; max. value = 60, with higher values reflecting more manic symptoms) | 6 months (12 months for a subgroup of participants) | 
| General functioning | General functioning assessed by the Functional Assessment Short Test, a 24-item interviewer-administered interview concerning autonomy, occupational functioning, cognitive functioning, financial issues, interpersonal relationships and leisure time (min. value = 0; max. value = 72, with higher values reflecting poorer function) | 6 months (12 months for a subgroup of participants) | 
| Self-rated quality of life | Self-rated quality of life assessed by completion of the WHO Quality of Life-BREF questionnaire. (Min. value = 9; max. value = 45, with higher values reflecting better quality of life) | Changes between baseline levels, 3 and 6 months (12 months for a subgroup of participants) | 
| Self-rated perceived stress level | Self-rated stress level assessed by completion of Cohen's Perceived Stress Scale, a 10-item questionnaire. (Min. value = 0; max. value = 40, with higher values reflecting increased stress level | Changes between baseline levels, 3 and 6 months (12 months for a subgroup of participants) | 
| Self-rated sleep quality | Self-rated sleep quality assessed by completion of the Pittsburgh Sleep Quality Index. This questionnaire does not use a predefined scale. | Changes between baseline levels, 3 and 6 months (12 months for a subgroup of participants) |