Efficacy and Safety Evaluation of Low-Dose Acetylsalicylic Acid as Adjunctive Therapy in Bipolar Affective Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial
- Trial ID
- 2024-516584-86-00
- Protocol
- IPIN/ASPIRIN/BD
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this multicentre, randomized, double-blind, placebo-controlled study is to evaluate the **efficacy** and **safety** of low-dose **acetylsalicylic acid** (150 mg/day) as an add-on treatment to standard therapy in patients with **Bipolar Affective Disorder**. This investigation is clinically relevant as it seeks to determine whether the addition of acetylsalicylic acid can enhance therapeutic outcomes in managing bipolar disorder, potentially offering a novel adjunctive treatment option. No secondary objectives are specified for this study.
Participants
The clinical trial focuses on individuals diagnosed with **Bipolar Affective Disorder**, specifically those experiencing a current episode of depression. The study population includes both male and female participants aged between 18 and 60 years. Participants are required to be currently undergoing treatment with at least one mood stabilizer, excluding valproates, and must have a body mass index (BMI) within the range of 18 to 40 kg/m². Women of childbearing potential must have a negative serum pregnancy test at screening and agree to use highly effective contraceptive methods during the study. The sponsor has not provided information regarding the total number of participants. The trial population was selected based on the ability to provide informed consent and meet specific health criteria, ensuring a focus on individuals who can safely participate in the study. Lifestyle considerations such as diet and physical activity are not specified, but the inclusion criteria emphasize the importance of stable health conditions and effective contraceptive use for women of childbearing age.
Plans and Procedures
The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the efficacy and safety of low-dose **acetylsalicylic acid** (150 mg/day) as an add-on treatment to standard therapy in patients with **bipolar disorder**. The trial is set to span a duration of approximately 12 months, with the estimated end date being April 30, 2026. Participants will be randomly assigned to receive either the active treatment or a placebo, ensuring that neither the participants nor the investigators are aware of the group assignments, thus maintaining the double-blind nature of the study.
The sequence of study visits begins with an inclusion (screening) visit, where eligibility criteria are assessed, including a confirmed diagnosis of bipolar disorder, a current episode of depression, and other health parameters such as age and body mass index. Following successful screening, participants will undergo regular follow-up visits at 2, 4, 6, and 12 months from baseline. These visits are designed to monitor the primary and secondary endpoints, which include changes in the Hamilton Depression Rating Scale (HAMD-17) scores, remission rates, and the frequency of suicide attempts, among others. The end-of-study visit will conclude the participant's involvement, where final assessments will be conducted to evaluate the long-term efficacy and safety of the treatment.
Participant involvement is expected to last for the entire 12-month duration of the trial, provided there are no conditions necessitating early termination. Such conditions may include adverse reactions to the treatment, withdrawal of consent, or any significant protocol deviations. The trial's methodology ensures rigorous monitoring and adherence to ethical standards, with the primary aim of advancing the understanding of treatment options for bipolar disorder.
Treatment
The clinical trial involves the administration of **acetylsalicylic acid** as an experimental medication. The product used is Polocard, which contains 150 mg of acetylsalicylic acid in the form of gastro-resistant tablets. The tablets are designed for **oral use**. The maximum daily dose is 150 mg, with a total maximum dose of 54,750 mg over a treatment period of up to 12 weeks. The active substance, acetylsalicylic acid, is of chemical origin and is provided by ZENTIVA, K.S. Compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the treatment regimen.
The study also includes a **placebo** as a non-experimental treatment. The placebo is used as a comparator to evaluate the efficacy and safety of the experimental medication. The placebo is administered in a similar pharmaceutical form and route as the active treatment to maintain the double-blind nature of the study. Participants will receive either the active treatment or the placebo in a randomized manner, and the administration schedule will mirror that of the active treatment to ensure consistency across the study groups.
Efficacy
The efficacy of low-dose **acetylsalicylic acid** as an add-on treatment for bipolar disorder will be assessed using both primary and secondary endpoints. The primary endpoints include the change in the Hamilton Depression Rating Scale (HAMD-17) score after 2 months for short-term intervention and relapse rates for a disease episode or worsening rates at 4, 6, and 12 months for long-term intervention. Secondary endpoints for short-term intervention involve remission rates defined as 7 or fewer points on the HAMD-17 scale, remission rates on both the HAMD-17 and the Mania Young Scale (YMRS), percentages of clinically significant improvement based on a 50% reduction in HAMD-17 score, changes in the Clinical Global Impression Scale - Improvement (CGI-I), changes in the Global Assessment of Functioning (GAF) scale, and the frequency of suicide attempts after 2 months. For long-term intervention, secondary endpoints include similar measures at 4, 6, and 12 months.
These efficacy parameters will be measured and collected at specified timepoints, including 2 months for short-term and 4, 6, and 12 months for long-term interventions. The HAMD-17, YMRS, CGI-I, and GAF scales are the primary tools used for these assessments. The analysis will focus on comparing the efficacy of the treatment in the intervention group against the placebo group, with the aim of determining the effectiveness of low-dose acetylsalicylic acid in improving symptoms and preventing relapse in patients with bipolar disorder.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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);
- Current episode of depression (ICD-10 codes F31.3-F31.5);
- Age 18-60 years; women and men;
- Current treatment with at least one mood stabilizer recommended in bipolar disorder, except for valproates;
- The patient is able to give informed consent to participate in the study;
- 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).
- 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
- Coexisting severe mental disorders (schizophrenia, dementia, addiction, OCD, depression other than in the course of BD);
- Taking acetylsalicylic acid in a chronic manner due to somatic diseases;
- 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)
- Taking valproates within 7 days prior to the start of the study (due to the risk of significant interactions with ASA)
- Known allergy or hypersensitivity to ASA or other NSAIDs;
- Pregnant or breastfeeding women;
- 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);
- 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.
- 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.
- Current use of non-pharmacological treatments (psychotherapy and biological treatments, i.e. electroconvulsive therapy, phototherapy, deep brain stimulation, transcranial magnetic stimulation)
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Poland | Recruiting | 31 May 2022 | 100 |
Sites & Investigators
Research sites
Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Placebo | Placebo | N/A | — | — | — | N/A |
Polocard, 150 mg, tabletki dojelitowe | Test | TABLETKI DOJELITOWE | ORAL USE | 150 | 12 | PRD10007409 |