EVALUATION OF EFFICACY AND SAFETY OF LOW-DOSE NALTREXONE IN PATIENT WITH OSTEOARTHRITIS: A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 130
- 试验地点
- 2
- 主要终点
- • To evaluate the efficacy of add on low dose naltrexone against add on placebo in patients with knee osteoarthritis using reduction in the VAS score for 8 weeks.
研究概览
简要总结
Despite considerable progress in the field, the primary treatments for Osteoarthritis remain traditional.Existing medical treatments such as NSAIDs corticosteroids, and opioids mainly offer symptom relief without targeting the underlying causes of the condition. Although these drugs can provide temporary benefit, they are often associated with adverse effects like gastrointestinal, cardiovascular, and kidney complications, and opioids carry a risk of addiction. Moreover these treatments fall short in addressing the neuroinflammation and central pain sensitization that play a crucial role in the persistence and intensity of OA pain leaving many patients inadequately treated. In recent it has shown that in osteoarthritis there is activation of toll like receptor 4 or TLR4 in innate immune cells and further activation of NFkB pathway in leading to cytokine release and further damage. Low dose naltrexone or LDN represents a novel treatment strategy that targets both immune and nervous system pathways involved in chronic pain. In low doses, it briefly blocks opioid receptors, leading to a compensatory increase in the body’s natural opioid. Also dampen inflammation by inhibiting TLR4 and thereby suppressing microglial cell activity. This action decreases the production of inflammatory cytokines such as TNF alpha IL1beta and IL6 which are known to contribute to the development of osteoarthritis. LDN has demonstrated potential in managing various chronic pain and inflammatory conditions, with a favourable safety profile, low addiction risk and low cost. Its dual action on inflammation and nerve sensitization makes it a promising option for knee OA treatment. We hypothesise that LDN may act on TLR4 on peripheral innate immune cells and modulate the activity and decrease the pro inflammatory cytokines release in OA there for we propose this study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 45.00 Year(s) 至 75.00 Year(s)（—）
- 性别
- All
入选标准
- •Patients of either sex having age between 45 75 years with clinical diagnosis of knee osteoarthritis grade 1 or 2 according to Kellgren and Lawrence system for classification of osteoarthritis.
- •Patient with VAS score more than 2 out of
- •Patients who are willing to give informed written consent.
排除标准
- •Patient with history of hypersensitivity to naltrexone.
- •Patient on treatment with any type of prior opioid medication.
- •Patient with history of opioid or alcohol abuse.
- •Patient on treatment with systemic corticosteroid within the last 4 weeks.
- •Patient with diagnosis other than osteoarthritis.
- •Patient on treatment with intra-articular injection such as corticosteroids or hyaluronic acid.
- •Patient with abnormal liver functions with total bilirubin more than 2.5 mg per deciliter.
- •Patient with severe acute infection, uncontrolled diabetes mellitus congenital or acquired immunodeficiency liver cirrhosis severe cardiac disease or myocardial infarction in last 1 month.
- •Patients with blood hemoglobin levels less than 9 grams per dL, absolute lymphocyte count less than 500 cells and or absolute neutrophil count less than 1000 cells per cubic mm of blood.
- •Patient with abnormal renal or liver functions with creatinine more than 2 mg per deciliter or serum total cholesterol more than 200mg per dl).
- •Patient with severe active infection like active tuberculosis hepatitis B or C or positive HIV serology at screening.
- •Patient with known or suspected history of immunosuppression or history of opportunistic infections like tuberculosis histoplasmosis listeriosis coccidioidomycosis or aspergillosis.
结局指标
主要结局
• To evaluate the efficacy of add on low dose naltrexone against add on placebo in patients with knee osteoarthritis using reduction in the VAS score for 8 weeks.
时间窗: At baseline 4 and 8 weeks
次要结局
- • To compare the proportion of patients achieving WOMAC score 0 or a reduction of 10 grade from baseline(• To compare the percentage of patients with Oxford Knee Score (OKS) pain subscale of 28 or a 3-point reduction from baseline)
研究者
Debasish Hota
AIIMS Bhubaneswar 751019