Bipolar disorder MedDRA version: 21.1 Level: LLT Classification code 10004935 Term: Bipolar affective disorder, unspecified System Organ Class: 100000004873
Conditions
Interventions
Trade Name: Hjertemagnyl
Pharmaceutical Form: Capsule
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use
Sponsors
Copenhagen Affective Disorder research Center (CADIC),
Eligibility
Sex/Gender
All
Inclusion criteria
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) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 225 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 25
Exclusion criteria
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: o Reluctance to use effective contraception (IUD or hormonal contraception) during enrollment, including a safety period of one week following last medication day/trial completion o Pregnancy; pregnancy ruled out by HCG test before enrollment o 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective of the present study is to conduct an RCT investigating whether add-on low-dose Aspirin versus placebo add-on to standard treatment improves mood stabilization and other critical patient outcomes in subjects with BD, and whether its principal effects are antimanic, antidepressant or prophylactic against relapse. Primary hypothesis: Add on low dose aspirin versus placebo to standard treatment improves mood stabilization in BD;Secondary Objective: Secondary hypothesis: II. Associations between inflammatory markers and BD and treatment allocation a. Baseline inflammatory marker levels (hsCRP, cytokines ( IL-6, IL-10, IL-18, TNFr-alpha, etc., and hsCRP) and other inflammation-related biomarkers (oxidative stress, hair cortisol and gut microbiome composition) predict or moderate clinical improvement following treatment with low dose aspirin vs. placebo at t=3 months and t=6 months b. Changes in inflammatory markers represent indirect mediators of response, i.e. 1) allocated treatment affect inflammatory markers levels at t=3 months and t=6 months, and 2) inflammatory markers changes at t=3 months and t=6 months are associated with clinical outcome measures. III. Allocated treatment (low-dose aspirin versus placebo) improves cognition at t=3 months and t=6 months compared to t=0. IV. Baseline (before randomization) inflammatory marker levels are increased or altered in BD patients compared to HC;Primary end point(s): Mood stabilization will be measured by a mood instability score reflecting the daily variability in self-monitored mood as described in section ;Timepoint(s) of evaluation of this end point: Trial participation will include three visits (with an optional fourth visit for a subgroup of patients): An assessment at inclusion/baseline (T=0), one after three months (T=3), one after six months (T=6), and, for a subset of patients enrolled within the first trial year, we will also include an assessment at twelve months (T=12). S | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary/additional endpoints: 2. Associations between inflammatory markers and BD and treatment allocation: Level of inflammatory activity will be assessed by measuring inflammatory blood marker levels and other inflammation-related biomarkers (urinary oxidative stress, hair cortisol and gut microbiome composition): - Blood based biomarkers: High sensitive CRP (hsCRP), IL-6, IL-10, IL-18, TNF-alpha and BDNF. - Other inflammation-related biomarkers: o Urinary oxidative stress biomarker levels (oxidized nucleosides 8-oxodG and 9-oxoGuo) o Gut microbiome composition o Hair cortisol concentration 3. Allocated treatment (low-dose aspirin versus placebo) improves cognition at t=3 months and t=6 months compared to t=0 Cognition will be assessed by neuropsychological testing according to our newly developed Internet-based Cognition Assessment Tool (ICAT), which is self-administered by trial subjects in their home setting at start, midway and end of the RCT. The ICAT contains a set of five short tasks, representing different cognitive domains. Each subtest/task results in a score summing up to a total score. 4. Baseline (before randomization) inflammatory marker levels are increased or altered in BD subjects compared to healthy controls As described above 5. Additional endpoints a. Self-rated or observer-rated - Other daily self-reported smartphone-based data including daily activity level and sleep, as recently reported - Clinically rated observer-based scores at start, midway and end of the 6-month trial on the following three scales: Hamilton Depression Scale-6 items (HAM-D6) (being more sensitive in RCTs than the HAM-D17, the Young Mania Rating Scale (YMRS) and the Functional Assessment Short Test (FAST) (a 24-item interviewer-administered interview concerning autonomy, occupational functioning, cognitive functioning, financial issues, interpersonal relationships and leisure time) - Self-assessed scores on the following questionnair | — |
Countries
Denmark
Contacts
Public ContactCaroline Fussing Bruun
Copenhagen Affective Disorder research Center (CADIC),
Outcome results
None listed