Chronic Effects of Effective Oral Cannabidiol Delivery on 24-hour Ambulatory Blood Pressure and Vascular Outcomes in Treated and Untreated Hypertension: A Randomized, Placebo-controlled and Crossover Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 70
- 试验地点
- 2
- 主要终点
- 24-hour ambulatory blood pressure
研究概览
简要总结
The objective of this randomized, placebo-controlled and crossover study is to extend the findings from the acute studies into more chronic administration of CBD in individuals with mild or moderate hypertension who are either untreated or receiving standard care therapy. The hypothesis is that the hypotensive effects of CBD will be apparent in both untreated and treated hypertension and reflected in improved vascular biomarkers and psychological well-being.
详细描述
Research Design A double-blind, placebo-controlled, cross-over pilot study in which 60 volunteers (aged 40-70 years) will visit to laboratory on six occasions following an overnight fast. All participants will provide written informed consent. Eligible participants will then be randomized. The sequence of conditions the participant will receive will be generated by a research randomizer web-service (https://www.randomizer.org) and participants will complete: 1) placebo-control and 2) DehydraTECHTM CBD (225 to 300 mg split over three times daily for the initial 2.5 weeks and 375 to 450 mg split over three times for the following 2.5 weeks) - see "dosing" below for further details . Following a two-week washout, volunteers will then repeat testing for another five weeks under the different condition. The study design, implementation and reporting will following the CONSORT guidelines, including the 25-item checklist and a flow diagram.
DehydraTECH is a patented formulation processing technology developed by Lexaria Bioscience Corp. that has been shown to enhance the performance of lipophilic beneficial compounds in oral ingestible products by way of increased rate and extent of intestinal bioabsorption and systemic uptake. DehydraTECH formulations have been prepared with a range of lipophilic molecules of interest and administered orally to animals and/or humans to investigate pharmacokinetic and pharmacodynamic performance attributes. For example, in young healthy humans, DehydraTECH technology has been studied in an oral CBD formulation and shown to result in higher and more rapid levels of delivery that was reflected in lower blood pressure when compared to positive controls with matching CBD concentrations (Patrician et al., 2019). Moreover, in volunteers with pre-hypertension, there were significant reductions in systolic, mean arterial blood pressure and arterial stiffness over an ambulatory 24-hr monitoring period following administration of oral DehydraTECH2.0 (150 mgs per 8 hours totalling 450 mgs) when compared to placebo. The DehydraTECH2.0 CBD was well tolerated with no ill-reported effects.
Both researchers and subjects will be blinded to the performed conditions on testing days by having a research associate who is not involved in any other aspect of the study supply the capsules according to the randomization schedule. When reporting to the laboratory in the morning will be in the fasted state (no food or drinks for at least 10 hours).
Visit 1 - Screening
On the initial visit potential participants will read through the information and consent form, ask any questions, and provide written informed consent. Following informed consent the participants will complete a customized Medical and Health Status Questionnaire that will be used to assess inclusion/exclusion criteria and prior history of medical conditions. Thereafter, the following questionnaires will be completed: Memory Assessment Clinic questionnaire(MAC-Q); Beck Anxiety Inventory (BAI); Perceived Stress Scale Questionnaire (PSS); Short Form 36 Health Survey Questionnaire (SF-36); Beck Depression Inventory (BDI); Global Physical Activity Questionnaire (GPAQ); State trait Anxiety Inventory (STAI); Big Life sodium calculator (BLSC). Sleep Questionnaires, including the Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS); and the;); Stop-Bang Questionnaire (S-BANG).
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented or measured elevated blood pressure (120/80 to 139/80 mmHg), mild (stage 1) hypertension (140/90 to 159/99 mmHg) or moderate (stage 2) hypertension (160/100 to 179/109 mmHg)
- •Normal or overweight (body mass index 18.5 to 35.0 kg/m2)
- •The female subjects are considered post-menopausal, and therefore not of reproductive potential, if they have not menstruated for at least 24 consecutive months in the absence of medications known to induce amenorrhea.
- •Heterosexually active female subjects of reproductive potential must be on contraception management using at least one of the following methods while taking study drug and for 30 days following the last dose of study drug:
- •Barrier method of contraception [condoms (male or female), diaphragm, or cervical cap] with spermicide
- •Hormone-based oral, injectable, or implantable contraceptive
- •Bilateral tubal ligation/cauterization
- •Surgically sterile (hysterectomy or bilateral oophorectomy) or vasectomized male partner Undergo <150 minutes of moderate-to-vigorous activity per week Up to 40 subjects will be included who are not using anti-hypertensive therapy Up to 30 subjects will be included who are being treated with either (1) ACE inhibitors with or without diuretics or (2) ACE inhibitors with Calcium Channel blocker with or without diuretics.
排除标准
- •Current smoker or using vapor-based products; or a medical or recreational cannabis user.
- •Have kidney, liver disease (see below) or gastrointestinal disease (e.g., irritable bowel syndrome, celiac disease, Crohn's disease) or has had a cholecystectomy.
- •Suffering from chronic diarrhea. (defined as >3 times loose / watery bowel movements per day lasting for more than 7 days; and occurring at least 4 times per year)
- •Current diagnosis or history of any seizure disorder
- •have diabetes
- •cardiac instability / disease.
- •are pregnant or breast feeding, or plan to become pregnant
- •history of opioid use
- •Dual blood pressure therapy other than ACE inhibitors with diuretic use and ACE inhibitors with Calcium Channel blocker with or without diuretics (e.g., ACE inhibitors with beta blockers)
- •unwilling or unable to execute the informed consent documentation
- •Liver disease, including, taking valproate, confirmed on baseline blood biochemistry - exclusion of subjects that have > 1.5 upper limit of normal (ULN) for ALT or AST, TBL >ULN at baseline determined by local reference population values in Croatia:
- •ULN for ALT 48 IU/L
- •ULN for AST 38 IU/L
- •ULN for ALP 142 IU/L
- •ULN for total bilirubin (TBL) 20 umol/L
- •ULN for GGT IU/L 55
结局指标
主要结局
24-hour ambulatory blood pressure
时间窗: Through study completion, an average of 1 year
Measured by ambulatory blood pressure monitoring system
次要结局
- Geriatric depression(Through study completion, an average of 1 year)
- Circulating cannabidiol(Through study completion, an average of 1 year)
- Arterial stiffness(Through study completion, an average of 1 year)
- Volume of hippocampus(Through study completion, an average of 1 year)
- The burning of calories through physical activity(Through study completion, an average of 1 year)
- Number of awakenings(Through study completion, an average of 1 year)
- Total sleep time(Through study completion, an average of 1 year)
- Nitric oxide markers(Through study completion, an average of 1 year)
- Blood cholesterol concentration in serum(Through study completion, an average of 1 year)
- Catestatin concentration in serum(Through study completion, an average of 1 year)
- Liver enzymes in serum(Through study completion, an average of 1 year)
- Total wake time(Through study completion, an average of 1 year)
- Blood flow through a. carotis interna(Through study completion, an average of 1 year)
- Salt intake(Through study completion, an average of 1 year)
- Sleep quality(Through study completion, an average of 1 year)
- C-reactive protein concentration in serum(Through study completion, an average of 1 year)
- Heart rate(Through study completion, an average of 1 year)
- Sleepiness(Through study completion, an average of 1 year)
- General health(Through study completion, an average of 1 year)
- Obstructive sleep apnea risk(Through study completion, an average of 1 year)
- Depression(Through study completion, an average of 1 year)
- Physical activity(Through study completion, an average of 1 year)
- Memory(Through study completion, an average of 1 year)
- Perceived stress(Through study completion, an average of 1 year)
- Anxiety(Through study completion, an average of 1 year)
研究者
Zeljko Dujic
Professor
University of Split, School of Medicine