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

Bipolar Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05035316
• Other study ID #: H-21014515
• Secondary ID: 2021-000862-14
• Status: Recruiting
• Phase: Phase 2
• Start date: January 20, 2022
• Est. completion date: December 1, 2024

Study information

• Verified date: January 2024
• Source: Mental Health Services in the Capital Region, Denmark
• Contact: Lars V Kessing, Prof
• Phone: +4538647081
• Email: lars.vedel.kessing[@]regionh.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 250
• Est. completion date: December 1, 2024
• Est. primary completion date: December 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Bipolar Disorder

Intervention

Drug:
• acetylsalicylic acid
Oral tablet: acetylsalicylic acid,150 mg, 1 tablet/day
• Calcium
Oral tablet: calcium, 1 tablet/day

Locations

Country	Name	City	State
Denmark	Psychiatric Center Copenhagen	Copenhagen

Sponsors (1)

Lead Sponsor	Collaborator
Lars Vedel Kessing

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Automatically smartphone-generated data	Level of physical activity measured by an accelerometer, social activity expressed as numbers of outgoing and incoming calls and text messages/24h, and time spent on the smartphone	6 months
Other	Cognition	Cognition is assessed at baseline and at 6 months follow-up according to the clinician-administered Screen for Cognitive Impairment in Psychiatry tool.	Changes between baseline score and score at 6 months-follow-up
Other	Manic symptoms	Manic symptoms assessed by the Young Mania Rating Scale (min. value = 0; max. value = 60, with higher values reflecting more manic symptoms)	Changes between baseline levels, 3 and 6 months
Other	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
Other	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)	Changes between baseline levels, 3 and 6 months
Other	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
Other	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
Other	Self-reported hours of sleep	Daily self-reported hours of sleep collected via the Monsenso-App.	6 months
Other	Hair cortisol	Exploratory outcome: systemic cortisol levels measured expressed by hair cortisol	Changes between baseline levels, 3 and 6 months follow-up
Other	Dysbiosis and short-chain fatty acid levels	As an exploratory outcome, stool samples will be analyzed to investigate the effects of LDA on dysbiosis and short-chain fatty acid levels	Difference between the two treatment arms at 6 months follow-up
Other	Blood-based biomarkers of inflammation and oxidative stress	As an exploratory outcome, we plan to measure the following blood-based biomarkers: hsCRP, cytokine profiling using mesoscale technology and soluble urokinase plasminogen activator receptor (suPAR) as markers of different aspects of inflammation; malondialdehyde, a marker of lipid peroxidation and oxidative stress; brain-derived neurotrophic factor	Changes between baseline and 6 months follow-up
Primary	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	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)	Changes between baseline score and score at 6 months-follow-up
Secondary	Daily self-reported activity instability	Daily self-reported activity instability collected via the Monsenso App	Changes between baseline score and score at 6 months-follow-up