Safety, Tolerability and Behavioural Effects of Souroubea-Platanus in Healthy Volunteers

NCT03904511 | Completed Phase 1

• 1 other identifier: 2018005
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Anxiety; Stress, Psychological

Outcome Measures

Primary Outcomes (33)

• Weight

  Participant weight (kilograms)

  Change from baseline weight (screening) in kg until day 14 of the protocol.

• Heart rate

  Heart rate (bpm)

  Change from baseline (screening) bpm until day 14 of the protocol.

• Blood pressure

  Systolic and Diastolic Blood pressure (mmhg)

  Change from baseline (screening) blood pressure until day 14 of the protocol.

• Body temperature

  Body temperature (degrees Fahrenheit).

  Change from baseline (screening) body temperature in degrees Fahrenheit until day 14 of the protocol.

• White blood cell (WBC) count (per L)

  White blood cell (WBC) count (per L)

  Change from baseline (screening) in any parameters until day 14 of the protocol.

• Red blood cell (RBC) count (per L)

  Red blood cell (RBC) count (per L)

  Change from baseline (screening) in any parameters until day 14 of the protocol.

• Hemoglobin (g/L)

  Hemoglobin (g/L)

  Change from baseline (screening) in any parameters until day 14 of the protocol.

• Hematocrit (vol%)

  Hematocrit (vol%)

  Change from baseline (screening) in any parameters until day 14 of the protocol.

• Platelet count (per L)

  Platelet count (per L)

  Change from baseline (screening) in any parameters until day 14 of the protocol.

• Blood Glucose (mg/dL)

  Blood Glucose (mg/dL)

  Change from baseline (screening) in any parameters until day 14 of the protocol.

• Serum calcium (mg/dL)

  Serum calcium (mg/dL)

  Change from baseline (screening) in any parameters until day 14 of the protocol.

• Serum potassium (mEq/L)

  Serum potassium (mEq/L)

  Change from baseline (screening) in any parameters until day 14 of the protocol.

• Serum sodium (mEq/L)

  Serum sodium (mEq/L)

  Change from baseline (screening) in any parameters until day 14 of the protocol.

• Serum chloride (mEq/L)

  Serum chloride (mEq/L)

  Change from baseline (screening) in any parameters until day 14 of the protocol.

• BUN; blood urea nitrogen (mg/dL)

  BUN; blood urea nitrogen (mg/dL)

  Change from baseline (screening) in any parameters until day 14 of the protocol.

• Creatinine (mg/dL)

  Creatinine (mg/dL)

  Change from baseline (screening) in any parameters until day 14 of the protocol.

• Serum albumin (g/dL)

  Serum albumin (g/dL)

  Change from baseline (screening) in any parameters until day 14 of the protocol.

• Serum total protein (g/dL)

  Serum total protein (g/dL)

  Change from baseline (screening) in any parameters until day 14 of the protocol.

• Serum ALP; Alkaline phosphatase (U/L)

  Serum ALP; Alkaline phosphatase (U/L)

  Change from baseline (screening) in any parameters until day 14 of the protocol.

• Serum GGT; Gamma glutamyl transferase (U/L)

  Serum GGT; Gamma glutamyl transferase (U/L)

  Change from baseline (screening) in any parameters until day 14 of the protocol.

• Serum AST; Aspartate aminotransferase (U/L)

  Serum AST; Aspartate aminotransferase (U/L)

  Change from baseline (screening) in any parameters until day 14 of the protocol.

• Serum ALT ; Alanine aminotransferase (U/L)

  Serum ALT ; Alanine aminotransferase (U/L)

  Change from baseline (screening) in any parameters until day 14 of the protocol.

• Serum CK; Creatinine Kinase (U/L)

  Serum CK; Creatinine Kinase (U/L)

  Change from baseline (screening) in any parameters until day 14 of the protocol.

• Serum Bilirubin (mg/dL)

  Serum Bilirubin (mg/dL)

  Change from baseline (screening) in any parameters until day 14 of the protocol.

• Urinary Glucose (mmol/L)

  Urinary Glucose (mmol/L)

  Change from baseline (screening) until day 14 of the protocol.

• Urinary ketones (mg/dL)

  Urinary ketones (mg/dL)

  Change from baseline (screening) until day 14 of the protocol.

• Urinary protein (mg/dL)

  Urinary protein (mg/dL)

  Change from baseline (screening) until day 14 of the protocol.

• Urinalysis; visual inspection

  Urinalysis; visual inspection, and microscopic visual examination if abnormal results present during visual inspection or on any of the chemistry panels.

  Change from baseline (screening) until day 14 of the protocol.

• Urinary pH

  Urinary pH

  Change from baseline (screening) until day 14 of the protocol.

• Urinary leukocytes (U/L)

  Urinary leukocytes (U/L)

  Change from baseline (screening) until day 14 of the protocol.

• UBG; Urobilinogen (mg/dL)

  UBG; Urobilinogen (mg/dL)

  Change from baseline (screening) until day 14 of the protocol.

• Urinary nitrites

  Urinary nitrites

  Change from baseline (screening) until day 14 of the protocol.

• Urinary specific gravity (S.G.)

  Urinary specific gravity (S.G.)

  Change from baseline (screening) until day 14 of the protocol.

Secondary Outcomes (3)

• 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.

Study Arms (3)

Low Dose Souroubea-Platanus

EXPERIMENTAL

190 mg souroubea-platanus preparation in vegicap. Administered once daily for 14 days.

Other: Souroubea-Platanus Preparation

High Dose Souroubea-Platanus

EXPERIMENTAL

380 mg souroubea-platanus preparation in vegicap. Administered once daily for 14 days.

Other: Souroubea-Platanus Preparation

Placebo

PLACEBO COMPARATOR

Inert placebo in an identical vegicap to the experimental treatment groups. Administered once daily for 14 days.

Other: Placebo

Interventions

Souroubea-Platanus Preparation OTHER

Extracts of S. Sympetala and P. occidentalis.

High Dose Souroubea-Platanus; Low Dose Souroubea-Platanus

Placebo OTHER

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 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

Sponsors & Collaborators

• University of Ottawa: lead
• Souroubea Botanicals Inc.: collaborator

Study Sites (1)

The Royal's Institute of Mental Health Research (IMHR) affiliated with the University of Ottawa

Ottawa, Ontario, K1Z 7K4, Canada

Location

Related Publications (18)

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• Crandon L. Why susto. Ethnology 1983;22:153-167.

  BACKGROUND

• Klein J. Susto: the anthropological study of diseases of adaptation. Soc Sci Med (1967). 1978 Jan;12(1B):23-8. No abstract available.

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• Rubel AJ. The epidemiology of a folk illness: Susto in Hispanic America. Ethnology 1964;3:268-283.

  BACKGROUND

• Signorini I. Patterns of fright: multiple concepts of susto in a Nahua-Ladino Community of the Sierra de Puebla (Mexico). Ethnology 1982;21:313-323.

  BACKGROUND

• Bourbonnais-Spear N. Ethnobotany and ethnopharmacology of Q'eqchi'Maya medicinal plants from southern Belize used for ethnopsychiatric and neurological purposes. University of Ottawa (Canada), 2005.

  BACKGROUND

• Puniani E, Cayer C, Kent P, Mullally M, Sanchez-Vindas P, Poveda Alvarez L, Cal V, Merali Z, Arnason JT, Durst T. Ethnopharmacology of Souroubea sympetala and Souroubea gilgii (Marcgraviaceae) and identification of betulinic acid as an anxiolytic principle. Phytochemistry. 2015 May;113:73-8. doi: 10.1016/j.phytochem.2014.02.017. Epub 2014 Mar 15.

  PMID: 24641939 BACKGROUND

• Mullally M, Mimeault C, Rojas MO, Vindas PS, Garcia M, Alvarez LP, et al. A botanical extract of Souroubea sympetala and its active principle, betulinic acid, attenuate the cortisol response to a stressor in rainbow trout, Oncorhynchus mykiss. Aquaculture 2017;468:26-31.

  BACKGROUND

• Mullally M, Cayer C, Kramp K, Otarola Rojas M, Sanchez Vindas P, Garcia M, Poveda Alvarez L, Durst T, Merali Z, Trudeau VL, Arnason JT. Souroubea sympetala (Marcgraviaceae): a medicinal plant that exerts anxiolysis through interaction with the GABAA benzodiazepine receptor. Can J Physiol Pharmacol. 2014 Sep;92(9):758-64. doi: 10.1139/cjpp-2014-0213. Epub 2014 Jul 28.

  PMID: 25140794 BACKGROUND

• Cayer C. In vivo behavioural characterization of anxiolytic botanicals: Souroubea sympetala. PhD Thesis. Masters Thesis submitted to the University of Ottawa, 2011.

  BACKGROUND

• Kessler RC, Soukup J, Davis RB, Foster DF, Wilkey SA, Van Rompay MI, Eisenberg DM. The use of complementary and alternative therapies to treat anxiety and depression in the United States. Am J Psychiatry. 2001 Feb;158(2):289-94. doi: 10.1176/appi.ajp.158.2.289.

  PMID: 11156813 BACKGROUND

• Villalobos P, Baker J, Sanchez Vindas P, Durst T, Masic A, Arnason JT. Clinical Observations and Safety Profile of Oral Herbal Products, Souroubea and Platanus Spp; a Pilot-Toxicology Study in Dogs. Acta Vet (Beogr) 2014;64:269-275.

  BACKGROUND

• Masic A, Liu R, Simkus K, Wilson J, Baker J, Sanchez P, Saleem A, Harris CC, Durst T, Arnason JT. Safety evaluation of a new anxiolytic product containing botanicals Souroubea spp. and Platanus spp. in dogs. Can J Vet Res. 2018 Jan;82(1):3-11.

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• Liu R, Ahmed F, Cayer C, Mullally M, Carballo AF, Rojas MO, Garcia M, Baker J, Masic A, Sanchez PE, Poveda L, Merali Z, Durst T, Arnason JT. New Botanical Anxiolytics for Use in Companion Animals and Humans. AAPS J. 2017 Nov;19(6):1626-1631. doi: 10.1208/s12248-017-0144-y. Epub 2017 Sep 11.

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  PMID: 1675690 BACKGROUND

• Mullally M, Kramp K, Cayer C, Saleem A, Ahmed F, McRae C, Baker J, Goulah A, Otorola M, Sanchez P, Garcia M, Poveda L, Merali Z, Durst T, Trudeau VL, Arnason JT. Anxiolytic activity of a supercritical carbon dioxide extract of Souroubea sympetala (Marcgraviaceae). Phytother Res. 2011 Feb;25(2):264-70. doi: 10.1002/ptr.3246.

  PMID: 20648677 BACKGROUND

MeSH Terms

Conditions

Anxiety Disorders; Stress, Psychological

Condition Hierarchy (Ancestors)

Mental Disorders; Behavioral Symptoms; Behavior

Study Officials

• Jakov Shlik, MD

  University of Ottawa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Director, OSI Clinic at The Royal

Study Record Dates

• First Submitted: March 16, 2019
• First Posted: April 5, 2019
• Study Start: May 15, 2019
• Primary Completion: December 31, 2019
• Study Completion: February 1, 2020
• Last Updated: February 11, 2020

Record last verified: 2020-02

Locations

CA (1)