Gut Microbiota, Pharmacogenetics and Integrase Strand Transfer Inhibitors Response
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 180
- 试验地点
- 1
- 主要终点
- Change in weight
研究概览
简要总结
This is an interventional phase IV trial enrolling HIV-infected patients treated by dolutegravir or bictegravir-based combined antiretroviral therapy, and patients with a planned shift to a dolutegravir or bictegravir-based combined antiretroviral therapy, that aims at understanding the individual response to dolutegravir and bictegravir, in terms of efficacy and toxicity.
详细描述
The main objective of our research project is to better define the inter-individual variability in terms of clinical and biological response towards Integrase Strand Transfer Inhibitors, an important ARV drug class used in the treatment of HIV infection. We aim at identifying predictors of drug efficacy and toxicity, which are eagerly awaited by clinicians as INSTIs are now prescribed worldwide and concerns about previously unidentified side effects are emerging.
The specific objectives of the project are:
- To study the impact of genetic polymorphisms in selected pharmacogenes (including genes coding for biotransformation enzymes and transport proteins) on INSTIs PK parameters and biomarkers relevant for TDM, such as trough (C0) and intracellular (IC) concentrations.
- To determine whether genetic polymorphisms in selected pharmacogenes might affect INSTIs efficacy, as assessed by the measurement of the viral load.
- To address the important question of the pathophysiological mechanisms lying behind the two main side effects of INSTIs, namely neuropsychiatric adverse events and abnormal weight gain.
- To describe how INSTIs affect the gut microbiome of treated patients, and to determine in turn how and by which pathways the gut microbiome might influence the clinical response (i.e. efficacy and toxicity) to INSTIs.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Pregnancy at the time of inclusion or expected pregnancy within 12 months, for patients treated by DTG or BIC during the study
- •Liver failure (Child-Pugh A, B or C)
研究组 & 干预措施
DTG treated (A)
80 HIV-infected adults treated with dolutegravir (as a component of their usual provider-prescribed antiretroviral regimen)
干预措施: Dolutegravir (Drug)
BIC treated (B)
30 HIV-infected adults treated with bictegravir (as a component of their usual provider-prescribed antiretroviral regimen)
干预措施: Bictegravir (Drug)
DTG discontinued due to neuropsychiatric adverse event (C)
50 HIV-infected adults having stopped dolutegravir due to neuropsychiatric adverse effects (insomnia, depression, anxiety)
干预措施: Dolutegravir (Drug)
Shifting to DTG (D)
20 virally controlled and immunologically functional HIV-infected adults shifting (as per standard care) from another ARV class to an antiretroviral regimen containing dolutegravir
干预措施: Dolutegravir (Drug)
Shifting to BIC (E)
20 virally controlled and immunologically functional HIV-infected adults shifting (as per standard care) from another ARV class to an antiretroviral regimen containing bictegravir
干预措施: Bictegravir (Drug)
结局指标
主要结局
Change in weight
时间窗: Through study completion, an average of 1 year
Overall weight change between treatment initiation through study completion
Change of psychometric evaluation (Hospital Anxiety and Depression Scale)
时间窗: Baseline and at 6 months
Change from baseline Hospital Anxiety and Depression Scale at 6 month after treatment initiation, for groups D and E. Hospital Anxiety and Depression Scale scores answers between 0 and 21 for its two compoinents, anxiety and depression. A higher score means a worse outcome.
Change of microbiota profile
时间窗: Baseline and at 6 months
Change from baseline microbiota profile at 6 month after treatment initiation, for groups D and E
Psychometric evaluation (Symptom-checklist-90-R)
时间窗: At least 3 months after the initiation of DTG/BIC
Psychometric evaluation through Symptom-checklist-90-R questionnaire, for groups A and B. The mean scores of each of the 10 subscales of Symptom-checklist-90-R will be calculated. A global severity index is computed as the average score of all 90 items. A higher score indicates a worse outcome.
Psychometric evaluation (Pichot's fatigue scale)
时间窗: At least 3 months after the initiation of DTG/BIC
Psychometric evaluation through Pichot's fatigue scale questionnaire, for groups A and B. Pichot's fatigue scale scores answers between 0 and 32. A higher score means a worse outcome.
Change of psychometric evaluation (Pittsburgh Sleep Quality Index)
时间窗: Baseline and at 6 months
Change from baseline Pittsburgh Sleep Quality Index at 6 month after treatment initiation, for groups D and E. Pittsburgh Sleep Quality Index scores answers from 0 to 21. A higher score means a worse outcome.
Dolutegravir and bictegravir through concentration
时间窗: 24 hours post last dose
Measurement of drug through concentration for groups A, B, D and E
Dolutegravir and bictegravir intracellular concentration
时间窗: 24 hours post last dose
Measurement of drug intracellular concentration for groups A, B, D and E
Viral replication
时间窗: At least 3 months after the initiation of DTG/BIC
Viral replication measured for groups A, B, D and E
Microbiota profile under treatment
时间窗: At least 6 months after the initiation of DTG/BIC
Determination microbiota profile for groups A, B, C, D and E
Change of psychometric evaluation (Symptom-checklist-90-R)
时间窗: Baseline and at 6 months
Change from baseline Symptom-checklist-90-R at 6 month after treatment initiation, for groups D and E. The mean scores of each of the 10 subscales of Symptom-checklist-90-R will be calculated. A global severity index is computed as the average score of all 90 items. A higher score indicates a worse outcome.
Psychometric evaluation (Pittsburgh Sleep Quality Index)
时间窗: At least 3 months after the initiation of DTG/BIC
Psychometric evaluation through Pittsburgh Sleep Quality Index questionnaire, for groups A and B. Pittsburgh Sleep Quality Index scores answers from 0 to 21. A higher score means a worse outcome.
Change of psychometric evaluation (Pichot's fatigue scale)
时间窗: Baseline and at 6 months
Change from baseline Pichot's fatigue scale at 6 month after treatment initiation, for groups D and E. Pichot's fatigue scale scores answers between 0 and 32. A higher score means a worse outcome.
Psychometric evaluation (Hospital Anxiety and Depression Scale)
时间窗: At least 3 months after the initiation of DTG/BIC
Psychometric evaluation through Hospital Anxiety and Depression Scale questionnaire, for groups A and B. Hospital Anxiety and Depression Scale scores answers between 0 and 21 for its two compoinents, anxiety and depression. A higher score means a worse outcome.
次要结局
未报告次要终点