Clinical trial NCT05035316: Effects of Low Dose Aspirin in Bipolar Disorder (The A-Bipolar RCT)
Official title: Effects of Low Dose Aspirin in Bipolar Disorder (The A-Bipolar RCT)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Bipolar Disorder
Lead sponsor: Mental Health Services in the Capital Region, Denmark
Sponsor class: OTHER
First posted: 2021-09-05
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blinded randomized placebo-controlled trial
Primary purpose: TREATMENT

Brief summary: 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: 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.

we wish to test the following hypotheses: Adding LDA versus placebo to standard drug treatment for BD will reduce 1) mood instability (MI), and 2) other critical outcomes such as activity instability and severity of depression.

Finally, we hypothesize that the reduction in MI is higher in patients with systemic inflammation at baseline indexed with the biomarkers high-sensitivity C-reactive protein (hsCRP), IL-6, and soluble urokinase plasminogen activator receptor (suPAR).

Eligibility criteria: Inclusion Criteria:

* Bipolar disorder (type 1 or 2), with diagnoses confirmed by SCAN interview.
* Age 18-65 years
* 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

Primary outcomes:
measure: Daily self-reported mood instability
timeFrame: 6 months (12 months for a subgroup of participants)
Secondary outcomes:
measure: Depressive symptoms
timeFrame: Changes between baseline score and score at 6 months-follow-up
measure: Daily self-reported activity instability
timeFrame: Changes between baseline score and score at 6 months-follow-up
Other outcomes:
measure: Automatically smartphone-generated data
timeFrame: 6 months
measure: Cognition
timeFrame: Changes between baseline score and score at 6 months-follow-up
measure: Manic symptoms
timeFrame: Changes between baseline levels, 3 and 6 months
measure: Self-rated sleep quality
timeFrame: Changes between baseline levels, 3 and 6 months
measure: General functioning
timeFrame: Changes between baseline levels, 3 and 6 months
measure: Self-rated perceived stress level
timeFrame: Changes between baseline levels, 3 and 6 months
measure: Self-rated quality of life
timeFrame: Changes between baseline levels, 3 and 6 months
measure: Self-reported hours of sleep
timeFrame: 6 months
measure: Hair cortisol
timeFrame: Changes between baseline levels, 3 and 6 months follow-up
measure: Dysbiosis and short-chain fatty acid levels
timeFrame: Difference between the two treatment arms at 6 months follow-up
measure: Blood-based biomarkers of inflammation and oxidative stress
timeFrame: Changes between baseline and 6 months follow-up
Locations:
city: Copenhagen
country: Denmark
facility: Psychiatric Center Copenhagen
Study officials:
References: