Clinical trial NCT03673930: Cognitive and Cerebral Blood Flow Effects of Zanthozylum Armatum Fruit Extract in Healthy Adults Aged 30 - 55
Official title: The Acute and Chronic Cognitive and Cerebral Blood Flow Effects of Zanthozylum Armatum Fruit Extract: a Double Blind, Randomized, Placebo Controlled, Parallel Groups Study in Healthy Humans
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cognitive Change
Keywords: NIRS
mood
cognitive performance
Zanthozylum armatum
Nepalese pepper
Lead sponsor: Northumbria University
Sponsor class: OTHER
Collaborators: name: Mibelle AG
First posted: 2018-09-17
Enrollment: 80
Sex: ALL
Minimum age (years): 30
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: Zanthozylum armatum (Z. armatum)-otherwise known as Nepalese pepper, or timut-is an perennial shrub found in India and across Southeast Asia. Preparations of the bark, fruit and seeds of Z. armatum have been extensively used in traditional Indian medicine. Preliminary data have indicated that preparations of Z. armatum may also be beneficial to cognitive function. The study aims to investigate the effects acute and chronic consumption of Z. armatum on cognitive function and cerebral blood flow.

Detailed description: Zanthozylum armatum (Z. armatum) is an perennial shrub found in India and across Southeast Asia. Preparations of the bark, fruit and seeds of Z. armatum have been extensively used in traditional Indian medicine. For example, the fruits and seeds have been employed as an aromatic tonic in fever and dyspepsia and the essential oil of the fruits has exhibited antibacterial, antifungal and anthelmintic properties. Furthermore, the dried fruits are used as spice, especially in Nepalese and Sichuan cuisine with increasing popularity across Europe. With regard to physiological effects relevant to brain function, Z. armatum has also been traditionally used as a cardio-depressant; these vasodilatory properties have recently being linked to its antagonistic effect on calcium ion channel function as demonstrated in isolated rabbit aorta tissue. In addition, the observed anti-inflammatory and antioxidant effects of preparations of Z. armatum may serve to beneficially impact cognition with chronic administration.

Although direct effects of Z. armatum on brain function have yet to be assessed; Zanthozylum fruit comprises one constituent of the traditional Japanese herbal medicine Daikenchuto (DKT) where some data do exist. In a series of trials investigating the effects of DKT on learning and memory function in mice, it was established that the extract of Zanthozylum fruit contained in DKT alone that was associated with reductions in escape latency in the Morris Water Maze task. Interestingly, the authors also revealed that it was the amide hydroxy-ɑ-sanshool (HAS) isolated from the Zanthozylum fruit extract that was associated with these effects, speculating that the effect of HAS on escape latencies was due to a facilitation effect of HAS on acetylcholine release.

Given the evidence of potentially relevant mechanisms of action and initial evidence of cognitive effects of HAS in murine models, the aim of this study is to assess the acute and chronic effects of Z. armatum on cognitive function, mood, and cerebral blood flow in healthy adults aged 30 to 55 years.

Eligibility criteria: Inclusion Criteria:

* Participants must self-assess themselves as being in good health
* Aged 30 to 55 years at the time of giving consent
* Are proficient in English equivalent to IELTS band 6 or above

Exclusion Criteria:

* Have any pre-existing medical condition/illness which will impact taking part in the study NOTE: the explicit exceptions to this are controlled (medicated) hypertension, arthritis, asthma, hay fever, high cholesterol and reflux-related conditions. There may be other, unforeseen, exceptions and these will be considered on a case-by-case basis; i.e. participants may be allowed to progress to screening if they have a condition/illness which would not interact with the active treatments or impede performance
* Are currently taking prescription medications or dietary supplements including omega fatty acids / fish oils NOTE: the explicit exceptions to this are hormone replacement treatments for female participants where symptoms are stable, those medications used in the treatment of arthritis, high blood pressure, high cholesterol and reflux-related conditions; and those taken 'as needed' in the treatment of asthma and hay fever. As above, there may be other instances of medication use which, where no interaction with the active treatments is likely, participants may be able to progress to screening
* Have planned a surgery requiring general anaesthesia
* Have high blood pressure (systolic over 159 mm Hg or diastolic over 99 mm Hg)
* Have a Body Mass Index (BMI) outside of the range 18-35 kg/m2
* Are pregnant, seeking to become pregnant or lactating
* Have learning difficulties, dyslexia
* Have a visual impairment that cannot be corrected with glasses or contact lenses (including colour-blindness)
* Smoker or regular consumption of nicotine containing products e.g. patches, gum, vaping
* Have a history of alcohol or drug abuse
* Excessive caffeine intake (\>500 mg per day)
* Have food intolerances/sensitivities, especially against citrus fruits
* Have any health condition that would prevent fulfilment of the study requirements
* Are unable to complete all of the study assessments
* Are currently participating in other clinical or nutrition intervention studies, or have in the past 4 weeks
* Do not have a bank account (required for payment)
* Are non-compliant with regards treatment consumption

Primary outcomes:
measure: Secondary memory score
timeFrame: Chronic (57 days)
Secondary outcomes:
measure: STAI-trait total score
timeFrame: Baseline
measure: STAI-state total score
timeFrame: Chronic (57 days)
measure: Secondary memory score
timeFrame: Acute (45, 180, 300 minutes post-dose)
measure: Secondary memory score
timeFrame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
measure: Working memory score
timeFrame: Chronic (57 days)
measure: Working memory score
timeFrame: Acute (45, 180, 300 minutes post-dose)
measure: Working memory score
timeFrame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
measure: Speed of memory score
timeFrame: Acute (45, 180, 300 minutes post-dose)
measure: Speed of memory score
timeFrame: Chronic (57 days)
measure: Speed of memory score
timeFrame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
measure: Accuracy of attention score
timeFrame: Acute (45, 180, 300 minutes post-dose)
measure: Accuracy of attention score
timeFrame: Chronic (57 days)
measure: Accuracy of attention score
timeFrame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
measure: Speed of attention score
timeFrame: Acute (45, 180, 300 minutes post-dose)
measure: Speed of attention score
timeFrame: Chronic (57 days)
measure: Speed of attention score
timeFrame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
measure: Immediate word recall task correctly identified words
timeFrame: Acute (45, 180, 300 minutes post-dose)
measure: Immediate word recall task correctly identified words
timeFrame: Chronic (57 days)
measure: Immediate word recall task correctly identified words
timeFrame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
measure: Immediate word recall task error responses
timeFrame: Acute (45, 180, 300 minutes post-dose)
measure: Immediate word recall task error responses
timeFrame: Chronic (57 days)
measure: Immediate word recall task error responses
timeFrame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
measure: Delayed word recall task correctly identified words
timeFrame: Acute (45, 180, 300 minutes post-dose)
measure: Delayed word recall task correctly identified words
timeFrame: Chronic (57 days)
measure: Delayed word recall task correctly identified words
timeFrame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
measure: Delayed word recall task correctly error responses
timeFrame: Acute (45, 180, 300 minutes post-dose)
measure: Delayed word recall task correctly error responses
timeFrame: Chronic (57 days)
measure: Delayed word recall task correctly error responses
timeFrame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
measure: Picture recognition accuracy
timeFrame: Acute (45, 180, 300 minutes post-dose)
measure: Picture recognition accuracy
timeFrame: Chronic (57 days)
measure: Picture recognition accuracy
timeFrame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
measure: Picture recognition reaction time
timeFrame: Acute (45, 180, 300 minutes post-dose)
measure: Picture recognition reaction time
timeFrame: Chronic (57 days)
measure: Picture recognition reaction time
timeFrame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
measure: Word recognition accuracy
timeFrame: Acute (45, 180, 300 minutes post-dose)
measure: Word recognition accuracy
timeFrame: Chronic (57 days)
measure: Word recognition accuracy
timeFrame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
measure: Word recognition reaction time
timeFrame: Acute (45, 180, 300 minutes post-dose)
measure: Word recognition reaction time
timeFrame: Chronic (57 days)
measure: Word recognition reaction time
timeFrame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
measure: Name to face recall correct responses
timeFrame: Acute (45, 180, 300 minutes post-dose)
measure: Name to face recall correct responses
timeFrame: Chronic (57 days)
measure: Name to face recall correct responses
timeFrame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
measure: Name to face recall reaction time
timeFrame: Acute (45, 180, 300 minutes post-dose)
measure: Name to face recall reaction time
timeFrame: Chronic (57 days)
measure: Name to face recall reaction time
timeFrame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
measure: Peg and ball task planning time
timeFrame: Acute (45, 180, 300 minutes post-dose)
measure: Peg and ball task planning time
timeFrame: Chronic (57 days)
measure: Peg and ball task planning time
timeFrame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
measure: Peg and ball task completion time
timeFrame: Acute (45, 180, 300 minutes post-dose)
measure: Peg and ball task completion time
timeFrame: Chronic (57 days)
measure: Peg and ball task completion time
timeFrame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
measure: Peg and ball task errors
timeFrame: Acute (45, 180, 300 minutes post-dose)
measure: Peg and ball task errors
timeFrame: Chronic (57 days)
measure: Peg and ball task errors
timeFrame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
measure: Corsi blocks accuracy
timeFrame: Acute (45, 180, 300 minutes post-dose)
measure: Corsi blocks accuracy
timeFrame: Chronic (57 days)
measure: Corsi blocks accuracy
timeFrame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
measure: Choice reaction time accuracy
timeFrame: Acute (45, 180, 300 minutes post-dose)
measure: Choice reaction time accuracy
timeFrame: Chronic (57 days)
measure: Choice reaction time accuracy
timeFrame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
measure: Choice reaction time reaction time
timeFrame: Acute (45, 180, 300 minutes post-dose)
measure: Choice reaction time reaction time
timeFrame: Chronic (57 days)
measure: Choice reaction time reaction time
timeFrame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
measure: Numeric working memory accuracy
timeFrame: Acute (45, 180, 300 minutes post-dose)
measure: Numeric working memory accuracy
timeFrame: Chronic (57 days)
measure: Numeric working memory accuracy
timeFrame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
measure: Numeric working memory reaction time
timeFrame: Acute (45, 180, 300 minutes post-dose)
measure: Numeric working memory reaction time
timeFrame: Chronic (57 days)
measure: Numeric working memory reaction time
timeFrame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
measure: Serial 3 subtractions total responses
timeFrame: Acute (45, 180, 300 minutes post-dose)
measure: Serial 3 subtractions total responses
timeFrame: Chronic (57 days)
measure: Serial 3 subtractions total responses
timeFrame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
measure: Serial 3 subtractions total error responses
timeFrame: Acute (45, 180, 300 minutes post-dose)
measure: Serial 3 subtractions total error responses
timeFrame: Chronic (57 days)
measure: Serial 3 subtractions total error responses
timeFrame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
measure: Serial 7 subtractions total responses
timeFrame: Acute (45, 180, 300 minutes post-dose)
measure: Serial 7 subtractions total responses
timeFrame: Chronic (57 days)
measure: Serial 7 subtractions total responses
timeFrame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
measure: Serial 7 subtractions total error responses
timeFrame: Acute (45, 180, 300 minutes post-dose)
measure: Serial 7 subtractions total error responses
timeFrame: Chronic (57 days)
measure: Serial 7 subtractions total error responses
timeFrame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
measure: Rapid visual information processing accuracy
timeFrame: Acute (45, 180, 300 minutes post-dose)
measure: Rapid visual information processing accuracy
timeFrame: Chronic (57 days)
measure: Rapid visual information processing accuracy
timeFrame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
measure: Rapid visual information processing reaction time
timeFrame: Acute (45, 180, 300 minutes post-dose)
measure: Rapid visual information processing reaction time
timeFrame: Chronic (57 days)
measure: Rapid visual information processing reaction time
timeFrame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
measure: Rapid visual information processing false alarms
timeFrame: Acute (45, 180, 300 minutes post-dose)
measure: Rapid visual information processing false alarms
timeFrame: Chronic (57 days)
measure: Rapid visual information processing false alarms
timeFrame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
measure: Mental fatigue
timeFrame: Acute (45, 180, 300 minutes post-dose)
measure: Mental fatigue
timeFrame: Chronic (57 days)
measure: Mental fatigue
timeFrame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
measure: Subjective mood - Alert
timeFrame: Acute (45, 180, 300 minutes post-dose)
measure: Subjective mood - Alert
timeFrame: Chronic (57 days)
measure: Subjective mood - Alert
timeFrame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
measure: Subjective mood - Content (visual analogue scale)
timeFrame: Acute (45, 180, 300 minutes post-dose)
measure: Subjective mood - Content
timeFrame: Chronic (57 days)
measure: Subjective mood - Content
timeFrame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
measure: Subjective mood - Calm
timeFrame: Acute (45, 180, 300 minutes post-dose)
measure: Subjective mood - Calm
timeFrame: Chronic (57 days)
measure: Subjective mood - Calm (Bond Lader visual analogue scale)
timeFrame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
measure: Cerebral blood flow during performance of cognitive tasks
timeFrame: Acute (120, 150 minutes post-dose)
measure: Cerebral blood flow during performance of cognitive tasks
timeFrame: Superimposed chronic (57 days plus 120, 150 minutes post-dose)
measure: Cerebral blood flow at rest
timeFrame: Acute (120, 150 minutes post-dose)
measure: Cerebral blood flow at rest
timeFrame: Chronic (57 days)
measure: Cerebral blood flow at rest
timeFrame: Superimposed chronic (57 days plus 120, 150 minutes post-dose)
Other outcomes:
Locations:
city: Newcastle upon Tyne
country: United Kingdom
facility: Northumbria university
state: Tyne And Wear
Study officials:
affiliation: Northumbria University
name: Philippa A Jackson, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gilani SN, Khan AU, Gilani AH. Pharmacological basis for the medicinal use of Zanthoxylum armatum in gut, airways and cardiovascular disorders. Phytother Res. 2010 Apr;24(4):553-8. doi: 10.1002/ptr.2979.
citation: Kalia NK, Singh B, Sood RP. A new amide from zanthoxylum armatum. J Nat Prod. 1999 Feb;62(2):311-2. doi: 10.1021/np980224j.
citation: Nakamura T, Komai N, Isogami I, Ueno K, Ikegami F, Ono K, Yano S. Memory and learning-enhancing effect of Daikenchuto, a traditional Japanese herbal medicine, in mice.Journal of Natural Medicines 60(1): 64-67, 2006