Study to evaluate the efficacy and safety of low-dose aspirin as an add-on to standard therapy in patients with bipolar disorder (ASPIRIN BD)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Instytut Psychiatrii I Neurologii

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

19 May 2023 → ongoing

Decision date (initial)

2024-08-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Agencja Badań Medycznych

External identifiers

EU CT number

2024-516584-86-00

EudraCT number

2021-006635-25

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

The main aim of the study is to assess the efficacy and safety of low-dose acetylsalicylic acid (150 mg / d) as an add-on treatment to standard therapy in the treatment of bipolar disorder.

Conditions and MedDRA coding

Bipolar Affective Disorder

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Diagnosis of bipolar disorder (criterion verified by the qualifying physician on the basis of clinical history and criteria included in the classification of diseases ICD-10, code F31);
2. Current episode of depression (ICD-10 codes F31.3-F31.5);
3. Age 18-60 years; women and men;
4. Current treatment with at least one mood stabilizer recommended in bipolar disorder, except for valproates;
5. The patient is able to give informed consent to participate in the study;
6. The patient's body mass index is within the appropriate range (BMI> 18 and <40 kg / m2, where BMI = body weight (kg) / [height (m)] 2).
7. In women of childbearing age, a negative serum pregnancy test at screening and agreement to use highly effective contraceptive methods during the study (Women of childbearing potential (WOCBP) is defined as any woman or adolescent who has begun menstruation. A postmenopausal woman is defined as a woman who is over the age of 45 and has not had a menstrual period for at least 12 months). *Due to enzyme induction, carbamazepine may cause hormonal contraception to be ineffective, so patients of childbearing age taking carbamazepine as standard therapy should be advised to use other effective methods of contraception.

Exclusion criteria 10

1. Coexisting severe mental disorders (schizophrenia, dementia, addiction, OCD, depression other than in the course of BD);
2. Taking acetylsalicylic acid in a chronic manner due to somatic diseases;
3. Regular use of steroid or non-steroidal anti-inflammatory drugs (occasional use of NSAIDs is allowed), methotrexate, digoxin, acetazolamide, antidiabetic drugs - insulin and drugs from the sulfonylurea group, anticoagulants (coumarin derivatives, heparin, oral anticoagulants from the group of non-vitamin K antagonists rivaroxaban, apixaban, dabigatran), thrombolytic or platelet aggregation drugs (ticlopidine, clopidogrel)
4. Taking valproates within 7 days prior to the start of the study (due to the risk of significant interactions with ASA)
5. Known allergy or hypersensitivity to ASA or other NSAIDs;
6. Pregnant or breastfeeding women;
7. Asthma, which, in the investigator's opinion, would increase the risk of an asthma attack; history of serious somatic disease (e.g. significant valvular heart disease, heart failure, hypertrophic cardiomyopathy, severe or worsening cardiomyopathy, clinically significant ECG abnormalities (defined as PR> 240msec, QRS complex> 110msec, QTcF> 500, ST segment depression) > 2 mm, ST-segment elevation> 1 mm, severe obstructive pulmonary disease, untreated thyroid disease, diagnosed HIV or hepatitis A, B or C, myocardial infarction in the last 6 months, insulin-dependent diabetes mellitus, gout). includes any somatic uncontrolled (in the last 3 months prior to study entry) disease states; a positive history of gastrointestinal, liver or kidney disease, or any other abnormal condition that impairs the function of these organs and may result in the possibility of altered absorption, excessive accumulation, or metabolic disorders or excretion of study medication. such as: history of major gastrointestinal surgery (e.g. gastrectomy, gastroenterostomy, bowel resection etc.) or a current diagnosis of an active gastrointestinal disease, gastric or duodenal ulceration, chronic gastrointestinal disease (e.g. ulcerative colitis, ileitis or gastrointestinal bleeding); liver damage, ie values ≥ 3 times the upper limit of normal for at least two of the following - ALT, ASP, LDH, alkaline phosphatase, or bilirubin; impaired renal function as indicated by clinically significant abnormalities for blood urea nitrogen (≥ 30 mg / dL) and creatinine (≥ 2 mg / dL), as well as by the presence of abnormal urine components (eg Albuminuria);
8. A patient who received any investigational drug not authorized in the country where the clinical trial is conducted within 30 days immediately before the start of the trial.
9. Patients with menorrhagia. Objectively heavy menstrual bleeding is defined as prolonged (>7 days) excessive blood loss of more than 80 mL per menstrual cycle. Clinical signs predictive of heavy menstrual bleeding include clots >2.5 cm in size, low serum ferritin levels, seepage and the need to change a sanitary pad or tampon more often than every hour, as well as menstrual bleeding.
10. Current use of non-pharmacological treatments (psychotherapy and biological treatments, i.e. electroconvulsive therapy, phototherapy, deep brain stimulation, transcranial magnetic stimulation)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Short-term intervention - treatment of a depressive episode in the course of bipolar disorder (2 months): Change in the score on the Hamilton scale (HAMD-17) after 2 months of the study
2. Long-term intervention - relapse prevention (12 months): Relapse rates for a disease episode (in patients who have remitted at least 8 weeks) or worsening rates (for patients who have remitted less than 8 weeks) at 4, 6, and 12 months from baseline.

Secondary endpoints 12

1. Short-term intervention: The rates of remission (depressive episode) in the compared groups after 2 months defined as 7 or less points on the HAMD-17 scale;
2. Short-term intervention: Remission rates (bipolar remission) in the compared groups after 2 months defined as 7 points or less on the HAMD-17 scale and 7 points or less on the Mania Young scale (YMRS);
3. Short-term intervention: Percentages of clinically significant improvement in the compared groups after 2 months - assessment based on the HAMD-17 score (reduction of the score by at least 50% from the baseline);
4. Short-term intervention: Change in Clinical Global Impression Scale - Improvement (CGI-I) score for improvement / worsening from previous score on the Clinical Global Impression Scale (CGI-I) after 2 months;
5. Short-term intervention: Change in the score on the scale assessing the general functioning of the patient in the compared groups after 2 months - GAF scale (global assessment of functioning) - global assessment of functioning;
6. Short-term intervention: Evaluation of the frequency of suicide attempts in the compared groups after 2 months.
7. Long-term intervention: The rates of remission (depressive episode) in the compared groups at 4, 6 and 12 months defined as 7 or less points on the HAMD-17 scale;
8. Long-term intervention: Remission rates (bipolar remission) in the compared groups after 4, 6 and 12 months defined as 7 points or less on the HAMD-17 scale and 7 points or less on the Mania Young scale (YMRS);
9. Long-term intervention: Percentages of clinically significant improvement in the compared groups after 4, 6 and 12 months - assessment based on the HAMD-17 score (reduction of the score by at least 50% from the baseline);
10. Long-term intervention: Change in the overall clinical impression score for improvement / worsening - Clinical Global Impression Scale - Improvement (CGI-I) at 4, 6 and 12 months
11. Long-term intervention: Change in the score on the scale assessing the general functioning of the patient in the compared groups after 4, 6 and 12 months - GAF scale (global assessment of functioning) - global assessment of functioning;
12. Long-term intervention: Assessment of the frequency of suicide attempts in the compared groups after 4, 6 and 12 months.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Instytut Psychiatrii I Neurologii

Sponsor organisation

Instytut Psychiatrii I Neurologii

Address

Ul. Jana III Sobieskiego 9

City

Warsaw

Postcode

02-957

Country

Poland

Scientific contact point

Organisation

Instytut Psychiatrii I Neurologii

Contact name

National Coordinating Investigator

Public contact point

Organisation

Instytut Psychiatrii I Neurologii

Contact name

National Coordinating Investigator

Third parties 2

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications