A Pharmacological Trial With Sativex® and Gentamicin for Optimized Phamacological Treatment of Older Patients With Focus on Appetite Stimulation and Renal Risk Drugs
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- Differences in the objective function value of the population-based pharmacokinetic model when implementing renal clearance assessed by measured GFR (mL/min), or GFR estimates based on different endogenous markers, as covariates on gentamicin clearance
研究概览
简要总结
Malnutrition and inappropriate prescribing of renally excreted drugs are common among older persons and are associated with severe consequences such as complicated courses of treatment, mortality, and reduced quality of life. The overall purpose of CanPan is to optimize treatment of older persons with malnutrition with a focus on appetite stimulation and optimized prescribing of renal risk drugs.
The CanPan trial consists of two sub-studies. Substudy 1 will provide knowledge on appetite and appetite stimulation and together, sub study 1 and 2 will offer unique knowledge on how body composition, renal function and biomarkers of organ function influence pharmacokinetics for a highly lipophilic (Sativex®) and hydrophilic (Hexamycin®) drug in older medical patients with malnutrition.
详细描述
The CanPan trial consists of sub study 1 and sub study 2. Subjects who meet all the inclusion criteria and none of the exclusion criteria are invited to participate in both sub studies. Sub study 1 consist of trial days 1 and 2 and sub study 2 consists of trial day 3.
Sub study 1:
Sub study 1 is a double-blinded, randomized, placebo-controlled, multidose, crossover trial that evaluates the appetite stimulating effect as well as the pharmacokinetics of Sativex®. The primary purpose of sub study 1 is to 1) uncover whether Sativex® has appetite stimulating properties defined as increased energy intake compared to placebo, 2) to develop a pharmacokinetic-pharmacodynamic model, and gain knowledge about the effect of Sativex® on other markers of appetite, the intraocular pressure of the eye and safety parameters.
In sub study 1, subjects receive both Sativex® and placebo. Both Sativex® and placebo are administered as an oromucosal spray. Sativex consists of 2.7 mg tetrahydrocannabinol (THC) and 2.5 mg cannabidiol (CBD) per dose of spray (Cannabis sativa L. extract, cannabis leaf and flower). Subjects receive three dose of spray two times during a trial day. Trial day 1 is planned <14 days after inclusion and there is a 2-week break between trial days 1 and 2 due to a wash-out period. Follow-up visits/phonecalls are made on days 1, 2 and 7 after trial days 1 and 2.
Sub study 2:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥65 years of age
- •Admitted to the acute medical department, Hvidovre Hospital
- •Can cooperate cognitively and physically (patient reported)
- •Low appetite/anorexia of ageing measures by SNAQ score ≤14
- •BMI ≤30 (screening)
- •Able to read and understand Danish
- •Postmenopausal defined as missed periods for at least 12 months before the start of the trial
排除标准
- •Regular use of medical cannabis (patient reported)
- •Use of medical cannabis within 14 days at baseline (patient reported)
- •Recognized or suspected psychotic illness in the subject or the subjects family (medical record and patient report)
- •Severe personality disorders (journal)
- •Significant psychiatric disorder in addition to mild to moderate depression (medical record)
- •Allergy to the ingredients of Sativex®, placebo and Hexamycin® (patient reported)
- •Terminal diagnosis (journal)
- •Liver transplant (journal)
- •Chronic eGFR ≤15 mL / min2 or dialysis treatment (medical record)
- •High risk of nephrotoxicity due to existing drug treatment (medical assessment)
- •Pacemaker (journal)
- •Epilepsy (journal)
- •Recurrent seizures (journal)
- •Uncontrolled hypertension (journal)
- •Food intolerance to the ingredients in the test meals (patient-reported)
- •Vegetarian and vegan (patient-reported)
- •Unwilling to avoid driving for up to 72 hours after administration of Sativex® (patient-reported)
- •Unwilling to avoid alcohol 24 hours up to test days (patient-reported)
- •Patients with ascites ( journal)
- •Patients with significant edema on the days of the trial (journal / visual inspection)
- •In active treatment of cancer or have disseminated cancer (journal)
- •Known with brain - or kidney tumor (journal)
- •Known with angina pectoris or intermittent claudication
- •Known with stroke, AMI, or heart failure (NYHA III-IV) within the past 5 years (journal)
- •In isolation
- •Obs. Covid-19
研究组 & 干预措施
Sativex first (blinded) (3 dose of spray)
Trial day 1: Sativex (3 dose of spray x 2) Trial day 2: Placebo (3 dose of spray x 2) Trial day 3: Voluntary
干预措施: Sativex (Drug)
Placebo first (blinded) (3 dose of spray)
Trial day 1: Placebo (3 dose of spray x 2) Trial day 2: Sativex (3 dose of spray x 2) Trial day 3: Voluntary
干预措施: Sativex (Drug)
结局指标
主要结局
Differences in the objective function value of the population-based pharmacokinetic model when implementing renal clearance assessed by measured GFR (mL/min), or GFR estimates based on different endogenous markers, as covariates on gentamicin clearance
时间窗: Trial day 3.
The objective function value (minus two times the log-likelihood) describes the prediction accuracy (goodness-of-fit) of a population pharmacokinetic model. A drop in the objective function value of 6.63 in a model with one (1) added covariate implemented on any specific parameter compared to a base model corresponds to a significant improvement in model fit with a p-value of 0.01 in a chi-squared test. Population-based pharmacokinetic modelling is an analysis method performed on pharmacokinetic data, i.e., plasma concentrations over time. Relevant pharmacokinetic parameters are estimated simultaneously by fitting the data to the model. The model structure is found through the analysis and determines which pharmacokinetic parameters are estimated. As a minimum, the clearance and distribution volume of the central compartment are estimated
Difference in energy intake (kJ) between Sativex® and placebo
时间窗: Trial days 1 and 2.
Measured at test meal
次要结局
- Change in the intraocular pressure of the eye between Sativex® and placebo(Trial days 1 and 2.)
- Safety parameter (cognition) for Sativex®(Trial days 1 and 2.)
- Differences in the objective function values of the population-based models of CBD and THC when implementing bodyweight, age, and body composition factors as covariates on the pharmacokinetic parameters of the model (e.g., clearance)(Trial days 1 and 2.)
- Difference in subjective appetite between Sativex® and placebo(Trial days 1 and 2.)
- Safety parameter (heart rate) for Sativex®(Trial days 1 and 2.)
- Correlation coefficient between clearance of gentamicin and clearance determined as mGFR or eGFR(Trial day 3.)
- Change in plasma creatinine µmol/L between baseline and 22 hours after administration of gentamicin(Trial day 3)
- Change in plasma cystatin C mg/L between baseline and 22 hours after administration of gentamicin(Trial day 3)
- Change in plasma NGAL ng/mL between baseline and 22 hours after administration of gentamicin(Trial day 3)
- Differences in the appetite hormones, total ghrelin and glucagon like peptide 1 (GLP-1) between Sativex® and placebo(Trial days 1 and 2.)
- Safety parameter (CNS effects) for Sativex®(Trial days 1 and 2.)
- Safety parameter (blood pressure) for Sativex®(Trial days 1 and 2.)
- Safety parameter (balance disorders) for Sativex®(Trial days 1 and 2.)
- Change in plasma KIM-1 pg/mL between baseline and 22 hours after administration of gentamicin(Trial day 3)
研究者
Ove Andersen
Research Director and Head of the Department of Clinical Research
Hvidovre University Hospital