Cognitive and Cerebral Blood Flow Effects of Zanthozylum Armatum Fruit Extract in Healthy Adults Aged 30 - 55

Cognitive Change Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03673930
• Other study ID #: 53BS1
• Status: Completed
• Phase: N/A
• Start date: April 6, 2018
• Est. completion date: November 16, 2018

Study information

• Verified date: January 2019
• Source: Northumbria University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: November 16, 2018
• Est. primary completion date: November 16, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 30 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Cognitive Change

Intervention

Dietary Supplement:
• Zanthozylum armatum
Zanthozylum armatum MCT oil extract
• Placebo
sunflower oil matched for appearance

Locations

Country	Name	City	State
United Kingdom	Northumbria university	Newcastle upon Tyne	Tyne And Wear

Sponsors (2)

Lead Sponsor	Collaborator
Northumbria University	Mibelle AG

Country where clinical trial is conducted

United Kingdom, 

References & Publications (3)

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. — View Citation

Kalia NK, Singh B, Sood RP. A new amide from zanthoxylum armatum . J Nat Prod. 1999 Feb;62(2):311-2. — View 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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Secondary memory score	This is a composite measure derived from summing the z score performance on the following cognitive tasks: immediate word recall, delayed word recall, delayed picture recognition, delayed word recognition, delayed name to face recall (-1 to 1 where higher is better).	Chronic (57 days)
Secondary	STAI-trait total score	State-trait anxiety inventory 'trait' score (20-80; higher is more anxious)	Baseline
Secondary	STAI-state total score	State-trait anxiety inventory 'state' score (20-80; higher is more anxious)	Chronic (57 days)
Secondary	Secondary memory score	This is a composite measure derived from summing the z score performance on the following cognitive tasks: immediate word recall, delayed word recall, delayed picture recognition, delayed word recognition, delayed name to face recall (-1 to 1 where higher is better).	Acute (45, 180, 300 minutes post-dose)
Secondary	Secondary memory score	This is a composite measure derived from summing the z score performance on the following cognitive tasks: immediate word recall, delayed word recall, delayed picture recognition, delayed word recognition, delayed name to face recall (-1 to 1 where 1 is better).	Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
Secondary	Working memory score	This is a composite measure derived from summing the z score performance on the numeric working memory task and Corsi block-tapping task (-1 to 1; where higher is better)	Chronic (57 days)
Secondary	Working memory score	This is a composite measure derived from summing the z score performance on the numeric working memory task and Corsi block-tapping task (-1 to 1; where higher is better)	Acute (45, 180, 300 minutes post-dose)
Secondary	Working memory score	This is a composite measure derived from summing the z score performance on the numeric working memory task and Corsi block-tapping task (-1 to 1; where higher is better)	Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
Secondary	Speed of memory score	This is a composite measure derived from summing the z score reaction times on the numeric working memory task, the delayed name/face recall task, the delayed picture recognition task, and the delayed word recognition task (-1 to 1; where lower is better).	Acute (45, 180, 300 minutes post-dose)
Secondary	Speed of memory score	This is a composite measure derived from summing the z score reaction times on the numeric working memory task, the delayed name/face recall task, the delayed picture recognition task, and the delayed word recognition task (-1 to 1; where lower is better)	Chronic (57 days)
Secondary	Speed of memory score	This is a composite measure derived from summing the z score reaction times on the numeric working memory task, the delayed name/face recall task, the delayed picture recognition task, and the delayed word recognition task (-1 to 1; where lower is better).	Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
Secondary	Accuracy of attention score	This is a composite measure derived from summing the z score accuracy performance on the choice reaction time and Rapid visual information processing tasks (-1 to 1; where higher is better)	Acute (45, 180, 300 minutes post-dose)
Secondary	Accuracy of attention score	This is a composite measure derived from summing the z score accuracy performance on the choice reaction time and Rapid visual information processing tasks (-1 to 1; where higher is better)	Chronic (57 days)
Secondary	Accuracy of attention score	This is a composite measure derived from summing the z score accuracy performance on the choice reaction time and Rapid visual information processing tasks (-1 to 1; where higher is better)	Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
Secondary	Speed of attention score	This is a composite measure derived from summing the z score reaction times on the choice reaction time and Rapid visual information processing tasks (-1 to 1; where lower is better)	Acute (45, 180, 300 minutes post-dose)
Secondary	Speed of attention score	This is a composite measure derived from summing the z score reaction times on the choice reaction time and Rapid visual information processing tasks (-1 to 1; where lower is better)	Chronic (57 days)
Secondary	Speed of attention score	This is a composite measure derived from summing the z score reaction times on the choice reaction time and Rapid visual information processing tasks (-1 to 1; where lower is better)	Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
Secondary	Immediate word recall task correctly identified words	total number (0-15; where higher is better)	Acute (45, 180, 300 minutes post-dose)
Secondary	Immediate word recall task correctly identified words	total number (0-15; where higher is better)	Chronic (57 days)
Secondary	Immediate word recall task correctly identified words	total number (0-15; where higher is better)	Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
Secondary	Immediate word recall task error responses	total number (can be any number; lower is better)	Acute (45, 180, 300 minutes post-dose)
Secondary	Immediate word recall task error responses	total number (can be any number; lower is better)	Chronic (57 days)
Secondary	Immediate word recall task error responses	total number (can be any number; lower is better)	Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
Secondary	Delayed word recall task correctly identified words	total number (0-15; where higher is better)	Acute (45, 180, 300 minutes post-dose)
Secondary	Delayed word recall task correctly identified words	total number (0-15; where higher is better)	Chronic (57 days)
Secondary	Delayed word recall task correctly identified words	total number (0-15; where higher is better)	Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
Secondary	Delayed word recall task correctly error responses	total number (can be any number; lower is better)	Acute (45, 180, 300 minutes post-dose)
Secondary	Delayed word recall task correctly error responses	total number (can be any number; lower is better)	Chronic (57 days)
Secondary	Delayed word recall task correctly error responses	total number (can be any number; lower is better)	Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
Secondary	Picture recognition accuracy	(%; 0-100; where higher is better)	Acute (45, 180, 300 minutes post-dose)
Secondary	Picture recognition accuracy	(%; 0-100; where higher is better)	Chronic (57 days)
Secondary	Picture recognition accuracy	(%; 0-100; where higher is better)	Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
Secondary	Picture recognition reaction time	(ms; lower is better)	Acute (45, 180, 300 minutes post-dose)
Secondary	Picture recognition reaction time	(ms; lower is better)	Chronic (57 days)
Secondary	Picture recognition reaction time	(ms; lower is better)	Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
Secondary	Word recognition accuracy	(%; 0-100; where higher is better)	Acute (45, 180, 300 minutes post-dose)
Secondary	Word recognition accuracy	(%; 0-100; where higher is better)	Chronic (57 days)
Secondary	Word recognition accuracy	(%; 0-100; where higher is better)	Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
Secondary	Word recognition reaction time	(ms; lower is better)	Acute (45, 180, 300 minutes post-dose)
Secondary	Word recognition reaction time	(ms; lower is better)	Chronic (57 days)
Secondary	Word recognition reaction time	(ms; lower is better)	Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
Secondary	Name to face recall correct responses	number (0-24; higher is better)	Acute (45, 180, 300 minutes post-dose)
Secondary	Name to face recall correct responses	number (0-24; higher is better)	Chronic (57 days)
Secondary	Name to face recall correct responses	number (0-24; higher is better)	Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
Secondary	Name to face recall reaction time	(ms; lower is better)	Acute (45, 180, 300 minutes post-dose)
Secondary	Name to face recall reaction time	(ms; lower is better)	Chronic (57 days)
Secondary	Name to face recall reaction time	(ms; lower is better)	Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
Secondary	Peg and ball task planning time	(ms; lower is better)	Acute (45, 180, 300 minutes post-dose)
Secondary	Peg and ball task planning time	(ms; lower is better)	Chronic (57 days)
Secondary	Peg and ball task planning time	(ms; lower is better)	Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
Secondary	Peg and ball task completion time	(ms; lower is better)	Acute (45, 180, 300 minutes post-dose)
Secondary	Peg and ball task completion time	(ms; lower is better)	Chronic (57 days)
Secondary	Peg and ball task completion time	(ms; lower is better)	Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
Secondary	Peg and ball task errors	number (can be any number, lower is better)	Acute (45, 180, 300 minutes post-dose)
Secondary	Peg and ball task errors	number (can be any number, lower is better)	Chronic (57 days)
Secondary	Peg and ball task errors	number (can be any number, lower is better)	Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
Secondary	Corsi blocks accuracy	Average scores from the last five correctly completed trials from the corsi block-tapping task	Acute (45, 180, 300 minutes post-dose)
Secondary	Corsi blocks accuracy	Average scores from the last five correctly completed trials from the corsi block-tapping task	Chronic (57 days)
Secondary	Corsi blocks accuracy	Average scores from the last five correctly completed trials from the corsi block-tapping task	Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
Secondary	Choice reaction time accuracy	(%; 0-100; where higher is better)	Acute (45, 180, 300 minutes post-dose)
Secondary	Choice reaction time accuracy	(%; 0-100; where higher is better)	Chronic (57 days)
Secondary	Choice reaction time accuracy	(%; 0-100; where higher is better)	Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
Secondary	Choice reaction time reaction time	(ms; lower is better)	Acute (45, 180, 300 minutes post-dose)
Secondary	Choice reaction time reaction time	(ms; lower is better)	Chronic (57 days)
Secondary	Choice reaction time reaction time	(ms; lower is better)	Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
Secondary	Numeric working memory accuracy	(ms; lower is better)	Acute (45, 180, 300 minutes post-dose)
Secondary	Numeric working memory accuracy	(%; 0-100; where higher is better)	Chronic (57 days)
Secondary	Numeric working memory accuracy	(%; 0-100; where higher is better)	Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
Secondary	Numeric working memory reaction time	(ms; lower is better)	Acute (45, 180, 300 minutes post-dose)
Secondary	Numeric working memory reaction time	(ms; lower is better)	Chronic (57 days)
Secondary	Numeric working memory reaction time	(ms; lower is better)	Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
Secondary	Serial 3 subtractions total responses	number - calculated from the 3 cycles of the Cognitive Demand Battery; higher is better	Acute (45, 180, 300 minutes post-dose)
Secondary	Serial 3 subtractions total responses	number - calculated from the 3 cycles of the Cognitive Demand Battery; higher is better	Chronic (57 days)
Secondary	Serial 3 subtractions total responses	number - calculated from the 3 cycles of the Cognitive Demand Battery; higher is better	Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
Secondary	Serial 3 subtractions total error responses	number - calculated from the 3 cycles of the Cognitive Demand Battery; lower is better	Acute (45, 180, 300 minutes post-dose)
Secondary	Serial 3 subtractions total error responses	number - calculated from the 3 cycles of the Cognitive Demand Battery; lower is better	Chronic (57 days)
Secondary	Serial 3 subtractions total error responses	number - calculated from the 3 cycles of the Cognitive Demand Battery; lower is better	Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
Secondary	Serial 7 subtractions total responses	number - calculated from the 3 cycles of the Cognitive Demand Battery; higher is better	Acute (45, 180, 300 minutes post-dose)
Secondary	Serial 7 subtractions total responses	number - calculated from the 3 cycles of the Cognitive Demand Battery; higher is better	Chronic (57 days)
Secondary	Serial 7 subtractions total responses	number - calculated from the 3 cycles of the Cognitive Demand Battery; higher is better	Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
Secondary	Serial 7 subtractions total error responses	number - calculated from the 3 cycles of the Cognitive Demand Battery; lower is better	Acute (45, 180, 300 minutes post-dose)
Secondary	Serial 7 subtractions total error responses	number - calculated from the 3 cycles of the Cognitive Demand Battery; lower is better	Chronic (57 days)
Secondary	Serial 7 subtractions total error responses	number - calculated from the 3 cycles of the Cognitive Demand Battery; lower is better	Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
Secondary	Rapid visual information processing accuracy	(%) - calculated from the 3 cycles of the Cognitive Demand Battery (%; 0-100; where higher is better)	Acute (45, 180, 300 minutes post-dose)
Secondary	Rapid visual information processing accuracy	(%) - calculated from the 3 cycles of the Cognitive Demand Battery (%; 0-100; where higher is better)	Chronic (57 days)
Secondary	Rapid visual information processing accuracy	(%) - calculated from the 3 cycles of the Cognitive Demand Battery (%; 0-100; where higher is better)	Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
Secondary	Rapid visual information processing reaction time	(ms) - calculated from the 3 cycles of the Cognitive Demand Battery; lower is better	Acute (45, 180, 300 minutes post-dose)
Secondary	Rapid visual information processing reaction time	(ms) - calculated from the 3 cycles of the Cognitive Demand Battery; lower is better	Chronic (57 days)
Secondary	Rapid visual information processing reaction time	(ms) - calculated from the 3 cycles of the Cognitive Demand Battery; lower is better	Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
Secondary	Rapid visual information processing false alarms	number - calculated from the 3 cycles of the Cognitive Demand Battery; lower is better	Acute (45, 180, 300 minutes post-dose)
Secondary	Rapid visual information processing false alarms	number - calculated from the 3 cycles of the Cognitive Demand Battery; lower is better	Chronic (57 days)
Secondary	Rapid visual information processing false alarms	number - calculated from the 3 cycles of the Cognitive Demand Battery; lower is better	Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
Secondary	Mental fatigue	visual analogue scale (%) - calculated from the 3 cycles of the Cognitive Demand Battery (0-100; higher indicates more fatigue)	Acute (45, 180, 300 minutes post-dose)
Secondary	Mental fatigue	visual analogue scale (%) - calculated from the 3 cycles of the Cognitive Demand Battery (0-100; higher indicates more fatigue)	Chronic (57 days)
Secondary	Mental fatigue	visual analogue scale (%) - calculated from the 3 cycles of the Cognitive Demand Battery (0-100; higher indicates more fatigue)	Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
Secondary	Subjective mood - Alert	derived from Bond Lader visual analogue scales (0-100; higher is more alert)	Acute (45, 180, 300 minutes post-dose)
Secondary	Subjective mood - Alert	derived from Bond Lader visual analogue scales (0-100; higher is more alert)	Chronic (57 days)
Secondary	Subjective mood - Alert	derived from Bond Lader visual analogue scales (0-100; higher is more alert)	Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
Secondary	Subjective mood - Content (visual analogue scale)	derived from Bond Lader visual analogue scales (0-100 higher is more content)	Acute (45, 180, 300 minutes post-dose)
Secondary	Subjective mood - Content	derived from Bond Lader visual analogue scales(0-100 higher is more content)	Chronic (57 days)
Secondary	Subjective mood - Content	derived from Bond Lader visual analogue scales(0-100 higher is more content)	Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
Secondary	Subjective mood - Calm	derived from Bond Lader visual analogue scales (0-100 higher is more calm)	Acute (45, 180, 300 minutes post-dose)
Secondary	Subjective mood - Calm	derived from Bond Lader visual analogue scale (0-100 higher is more calm)	Chronic (57 days)
Secondary	Subjective mood - Calm (Bond Lader visual analogue scale)	derived from Bond Lader visual analogue scale (0-100 higher is more calm)	Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)
Secondary	Cerebral blood flow during performance of cognitive tasks	Measured (in umol) using quantitative near infrared spectroscopy (higher indicates increased blood volume)	Acute (120, 150 minutes post-dose)
Secondary	Cerebral blood flow during performance of cognitive tasks	Measured (in umol) using quantitative near infrared spectroscopy (higher indicates increased blood volume)	Superimposed chronic (57 days plus 120, 150 minutes post-dose)
Secondary	Cerebral blood flow at rest	Measured (in umol) using quantitative near infrared spectroscopy (higher indicates increased blood volume)	Acute (120, 150 minutes post-dose)
Secondary	Cerebral blood flow at rest	Measured (in umol) using quantitative near infrared spectroscopy (higher indicates increased blood volume)	Chronic (57 days)
Secondary	Cerebral blood flow at rest	Measured (in umol) using quantitative near infrared spectroscopy (higher indicates increased blood volume)	Superimposed chronic (57 days plus 120, 150 minutes post-dose)

External Links

•   Link to study site website