Safety, Tolerability and Behavioural Effects of Souroubea-Platanus in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 45
- 试验地点
- 2
- 主要终点
- Urinary nitrites
研究概览
简要总结
Souroubea sympetala extracts have shown anxiolytic properties in animal models. Souroubea and its active principle betulinic acid appear to exert these effects by acting as an agonist for the benzodiazepine (BZD) binding site of the GABAA receptor with no withdrawal effects on food intake, locomotor activity, or other symptoms typically associated with BZD agonism. As such, this may offer a valuable source for an alternative anti-anxiety treatment.
The primary objective of this study is to (1) to evaluate the safety and tolerability of a single daily dose of an extract of a mixture of Souroubea spp. leaf and small branch material and Platanus spp. bark when administered orally over two weeks in healthy volunteers. Based on its safety in canine trials, we hypothesize that Souroubea-Platanus (SP) preparation will be well tolerated with adverse event profile similar to placebo.
The secondary objective is (2) to establish whether some of the anxiolytic properties of Souroubea-platanus seen in animal models will translate to human participants. We hypothesize that Souroubea-Platanus preparation will demonstrate anxiolytic and/or stress-reduction properties as indicated by salivary cortisol levels and self-report measures of anxiety.
详细描述
Background
Within Latin American indigenous communities tea brewed from fresh or dried crushed Souroubea leaves is used to treat Susto, a culture-bound syndrome resembling manifestations of Anxiety Disorders. Souroubea sympetala (Ss) leaf extract has shown to be effective as an anxiolytic in animal models, and betulinic acid (BA) is one of the active molecules responsible for mediating this effect.
Plant-based natural products are sought by many individuals as alternatives or supplements to standard medical care. As a result, more research is required in order to develop botanical treatments that are evidence-based, safe and guided by health practitioners. Souroubea-Platanus may offer such alternative.
Safety
Evidence suggests that Souroubea-Platanus was well tolerated in Beagles in a 28-day pilot study at 8x recommended dose, producing significant reductions in plasma cortisol 1h post-administration without any adverse reactions, except slightly reduced platelet count in 2 animals attributed to infection with Ehrlichia canis, likely contracted prior to the study onset. In a follow-up 16 beagles and up to 5x the recommended does for 28 days such decrease in platelet count was not observed, no there were any other adverse events. No adverse events have been reported in animals for the animal health product version of the drug (Zentrol) that has been on the market for 2 years. The naturalistic observations of Souroubea consumption suggest that it is safe for human use, however, this has not been established in a formal study. In addition, drug interactions have occurred with some herbal products, particularly those that strongly inhibit or induce CYP enzymes. As Souroubea may act on the BDZ binding site of the GABAA receptor, possible side-effects and symptoms similar to those associated with benzodiazepine anxiolytics are possible.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male and female participants aged 18-70 years
- •Females of childbearing potential must use reliable contraception during the study period; acceptable methods of birth control include all hormonal methods, IUDs, complete abstinence, effective physical barriers (e.g. condoms), or confirmed vasectomy of partner (if that information is volunteered by the participant)
- •Participants must be in good health status based on medical history and physical examination, including vital signs and clinical laboratory tests
- •Participants must refrain from taking any prescription or over the counter medication within the 14 days prior to the beginning of the study and during the study period
- •Participants must be non-smokers or light/occasional smokers (not more than 10 cigarettes per day)
- •Alcohol consumption should not exceed 3 drinks on any single day and no more than 7 drinks per week in women and no more than 4 drinks on any single day and no more than 14 drinks per week for men
- •BMI of 18.5-30 kg/m2 excluding markedly underweight and obese individuals
- •Participants must be willing to give written informed consent after the nature of the study has been fully explained
排除标准
- •Participants demonstrating uncontrolled clinically significant physical disease or abnormal laboratory test results within 14 days prior to the start of the study
- •Participants with current or history of alcohol or drug use disorder
- •Participants with any history of significant drug super-sensitivity, anaphylaxis, or anaphylactic reaction
- •Participants taking prescription medication or OTC medication within 14 days prior to inclusion
- •Participants who have a history of any significant psychiatric disorder or currently significant psychiatric symptoms
- •Participants with a family history of serious mental illness in first-degree relatives
- •Participants in a situation or having any condition which, in the opinion of the investigator, may interfere with optimal participation in the study
- •Participants testing positive for amphetamine, cannabinoids, cocaine, barbiturates, benzodiazepines, opioids or hallucinogens
- •Use of other non-prescription natural health products with known anti-anxiety effects
- •Known allergy to any of the medicinal and non-medicinal ingredients in any conditions of the study
结局指标
主要结局
Urinary nitrites
时间窗: Change from baseline (screening) until day 14 of the protocol.
Urinary nitrites
Creatinine (mg/dL)
时间窗: Change from baseline (screening) in any parameters until day 14 of the protocol.
Creatinine (mg/dL)
Serum total protein (g/dL)
时间窗: Change from baseline (screening) in any parameters until day 14 of the protocol.
Serum total protein (g/dL)
Serum ALP; Alkaline phosphatase (U/L)
时间窗: Change from baseline (screening) in any parameters until day 14 of the protocol.
Serum ALP; Alkaline phosphatase (U/L)
Urinary ketones (mg/dL)
时间窗: Change from baseline (screening) until day 14 of the protocol.
Urinary ketones (mg/dL)
Weight
时间窗: Change from baseline weight (screening) in kg until day 14 of the protocol.
Participant weight (kilograms)
Body temperature
时间窗: Change from baseline (screening) body temperature in degrees Fahrenheit until day 14 of the protocol.
Body temperature (degrees Fahrenheit).
Blood Glucose (mg/dL)
时间窗: Change from baseline (screening) in any parameters until day 14 of the protocol.
Blood Glucose (mg/dL)
Serum chloride (mEq/L)
时间窗: Change from baseline (screening) in any parameters until day 14 of the protocol.
Serum chloride (mEq/L)
Serum albumin (g/dL)
时间窗: Change from baseline (screening) in any parameters until day 14 of the protocol.
Serum albumin (g/dL)
Serum AST; Aspartate aminotransferase (U/L)
时间窗: Change from baseline (screening) in any parameters until day 14 of the protocol.
Serum AST; Aspartate aminotransferase (U/L)
Serum ALT ; Alanine aminotransferase (U/L)
时间窗: Change from baseline (screening) in any parameters until day 14 of the protocol.
Serum ALT ; Alanine aminotransferase (U/L)
Urinary Glucose (mmol/L)
时间窗: Change from baseline (screening) until day 14 of the protocol.
Urinary Glucose (mmol/L)
UBG; Urobilinogen (mg/dL)
时间窗: Change from baseline (screening) until day 14 of the protocol.
UBG; Urobilinogen (mg/dL)
Heart rate
时间窗: Change from baseline (screening) bpm until day 14 of the protocol.
Heart rate (bpm)
Blood pressure
时间窗: Change from baseline (screening) blood pressure until day 14 of the protocol.
Systolic and Diastolic Blood pressure (mmhg)
Hemoglobin (g/L)
时间窗: Change from baseline (screening) in any parameters until day 14 of the protocol.
Hemoglobin (g/L)
Hematocrit (vol%)
时间窗: Change from baseline (screening) in any parameters until day 14 of the protocol.
Hematocrit (vol%)
Platelet count (per L)
时间窗: Change from baseline (screening) in any parameters until day 14 of the protocol.
Platelet count (per L)
BUN; blood urea nitrogen (mg/dL)
时间窗: Change from baseline (screening) in any parameters until day 14 of the protocol.
BUN; blood urea nitrogen (mg/dL)
Serum GGT; Gamma glutamyl transferase (U/L)
时间窗: Change from baseline (screening) in any parameters until day 14 of the protocol.
Serum GGT; Gamma glutamyl transferase (U/L)
Urinary pH
时间窗: Change from baseline (screening) until day 14 of the protocol.
Urinary pH
White blood cell (WBC) count (per L)
时间窗: Change from baseline (screening) in any parameters until day 14 of the protocol.
White blood cell (WBC) count (per L)
Red blood cell (RBC) count (per L)
时间窗: Change from baseline (screening) in any parameters until day 14 of the protocol.
Red blood cell (RBC) count (per L)
Serum calcium (mg/dL)
时间窗: Change from baseline (screening) in any parameters until day 14 of the protocol.
Serum calcium (mg/dL)
Serum potassium (mEq/L)
时间窗: Change from baseline (screening) in any parameters until day 14 of the protocol.
Serum potassium (mEq/L)
Serum sodium (mEq/L)
时间窗: Change from baseline (screening) in any parameters until day 14 of the protocol.
Serum sodium (mEq/L)
Serum CK; Creatinine Kinase (U/L)
时间窗: Change from baseline (screening) in any parameters until day 14 of the protocol.
Serum CK; Creatinine Kinase (U/L)
Urinary protein (mg/dL)
时间窗: Change from baseline (screening) until day 14 of the protocol.
Urinary protein (mg/dL)
Serum Bilirubin (mg/dL)
时间窗: Change from baseline (screening) in any parameters until day 14 of the protocol.
Serum Bilirubin (mg/dL)
Urinalysis; visual inspection
时间窗: Change from baseline (screening) until day 14 of the protocol.
Urinalysis; visual inspection, and microscopic visual examination if abnormal results present during visual inspection or on any of the chemistry panels.
Urinary leukocytes (U/L)
时间窗: Change from baseline (screening) until day 14 of the protocol.
Urinary leukocytes (U/L)
Urinary specific gravity (S.G.)
时间窗: Change from baseline (screening) until day 14 of the protocol.
Urinary specific gravity (S.G.)
次要结局
- DSM-5 Self-rated Level 2 Anxiety(DSM-5 Self-rated Level 2 Anxiety to be completed on days 1, 7, and 14 of the 21-day protocol.)
- State-Trait Anxiety Inventory for Adults (STAI-AD)(Change from baseline until day 21 of the protocol.)
- Concentration of cortisol in saliva, measured in ng/sample(Change from baseline unil day 21 of the protocol.)
研究者
Jakov Shlik
Clinical Director, OSI Clinic at The Royal
University of Ottawa