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Completed

NCT Number: NCT03673930

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

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.

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Key information

Conditions

Cognitive Change

Age range

30 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Northumbria university

Newcastle upon Tyne, Tyne and Wear, NE1 8ST, United Kingdom

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Zanthozylum armatum

Dietary Supplement

Zanthozylum armatum MCT oil extract

Placebo

Dietary Supplement

sunflower oil matched for appearance

Primary outcomes

  1. Secondary memory score

    Time frame: Chronic (57 days)

    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).

Secondary outcomes

  1. STAI-trait total score

    Time frame: Baseline

    State-trait anxiety inventory 'trait' score (20-80; higher is more anxious)

  2. STAI-state total score

    Time frame: Chronic (57 days)

    State-trait anxiety inventory 'state' score (20-80; higher is more anxious)

  3. Secondary memory score

    Time frame: Acute (45, 180, 300 minutes post-dose)

    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).

  4. Secondary memory score

    Time frame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)

    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).

  5. Working memory score

    Time frame: Chronic (57 days)

    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)

  6. Working memory score

    Time frame: Acute (45, 180, 300 minutes post-dose)

    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)

  7. Working memory score

    Time frame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)

    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)

  8. Speed of memory score

    Time frame: Acute (45, 180, 300 minutes post-dose)

    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).

  9. Speed of memory score

    Time frame: Chronic (57 days)

    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)

  10. Speed of memory score

    Time frame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)

    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).

  11. Accuracy of attention score

    Time frame: Acute (45, 180, 300 minutes post-dose)

    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)

  12. Accuracy of attention score

    Time frame: Chronic (57 days)

    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)

  13. Accuracy of attention score

    Time frame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)

    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)

  14. Speed of attention score

    Time frame: Acute (45, 180, 300 minutes post-dose)

    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)

  15. Speed of attention score

    Time frame: Chronic (57 days)

    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)

  16. Speed of attention score

    Time frame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)

    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)

  17. Immediate word recall task correctly identified words

    Time frame: Acute (45, 180, 300 minutes post-dose)

    total number (0-15; where higher is better)

  18. Immediate word recall task correctly identified words

    Time frame: Chronic (57 days)

    total number (0-15; where higher is better)

  19. Immediate word recall task correctly identified words

    Time frame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)

    total number (0-15; where higher is better)

  20. Immediate word recall task error responses

    Time frame: Acute (45, 180, 300 minutes post-dose)

    total number (can be any number; lower is better)

  21. Immediate word recall task error responses

    Time frame: Chronic (57 days)

    total number (can be any number; lower is better)

  22. Immediate word recall task error responses

    Time frame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)

    total number (can be any number; lower is better)

  23. Delayed word recall task correctly identified words

    Time frame: Acute (45, 180, 300 minutes post-dose)

    total number (0-15; where higher is better)

  24. Delayed word recall task correctly identified words

    Time frame: Chronic (57 days)

    total number (0-15; where higher is better)

  25. Delayed word recall task correctly identified words

    Time frame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)

    total number (0-15; where higher is better)

  26. Delayed word recall task correctly error responses

    Time frame: Acute (45, 180, 300 minutes post-dose)

    total number (can be any number; lower is better)

  27. Delayed word recall task correctly error responses

    Time frame: Chronic (57 days)

    total number (can be any number; lower is better)

  28. Delayed word recall task correctly error responses

    Time frame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)

    total number (can be any number; lower is better)

  29. Picture recognition accuracy

    Time frame: Acute (45, 180, 300 minutes post-dose)

    (%; 0-100; where higher is better)

  30. Picture recognition accuracy

    Time frame: Chronic (57 days)

    (%; 0-100; where higher is better)

  31. Picture recognition accuracy

    Time frame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)

    (%; 0-100; where higher is better)

  32. Picture recognition reaction time

    Time frame: Acute (45, 180, 300 minutes post-dose)

    (ms; lower is better)

  33. Picture recognition reaction time

    Time frame: Chronic (57 days)

    (ms; lower is better)

  34. Picture recognition reaction time

    Time frame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)

    (ms; lower is better)

  35. Word recognition accuracy

    Time frame: Acute (45, 180, 300 minutes post-dose)

    (%; 0-100; where higher is better)

  36. Word recognition accuracy

    Time frame: Chronic (57 days)

    (%; 0-100; where higher is better)

  37. Word recognition accuracy

    Time frame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)

    (%; 0-100; where higher is better)

  38. Word recognition reaction time

    Time frame: Acute (45, 180, 300 minutes post-dose)

    (ms; lower is better)

  39. Word recognition reaction time

    Time frame: Chronic (57 days)

    (ms; lower is better)

  40. Word recognition reaction time

    Time frame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)

    (ms; lower is better)

  41. Name to face recall correct responses

    Time frame: Acute (45, 180, 300 minutes post-dose)

    number (0-24; higher is better)

  42. Name to face recall correct responses

    Time frame: Chronic (57 days)

    number (0-24; higher is better)

  43. Name to face recall correct responses

    Time frame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)

    number (0-24; higher is better)

  44. Name to face recall reaction time

    Time frame: Acute (45, 180, 300 minutes post-dose)

    (ms; lower is better)

  45. Name to face recall reaction time

    Time frame: Chronic (57 days)

    (ms; lower is better)

  46. Name to face recall reaction time

    Time frame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)

    (ms; lower is better)

  47. Peg and ball task planning time

    Time frame: Acute (45, 180, 300 minutes post-dose)

    (ms; lower is better)

  48. Peg and ball task planning time

    Time frame: Chronic (57 days)

    (ms; lower is better)

  49. Peg and ball task planning time

    Time frame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)

    (ms; lower is better)

  50. Peg and ball task completion time

    Time frame: Acute (45, 180, 300 minutes post-dose)

    (ms; lower is better)

  51. Peg and ball task completion time

    Time frame: Chronic (57 days)

    (ms; lower is better)

  52. Peg and ball task completion time

    Time frame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)

    (ms; lower is better)

  53. Peg and ball task errors

    Time frame: Acute (45, 180, 300 minutes post-dose)

    number (can be any number, lower is better)

  54. Peg and ball task errors

    Time frame: Chronic (57 days)

    number (can be any number, lower is better)

  55. Peg and ball task errors

    Time frame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)

    number (can be any number, lower is better)

  56. Corsi blocks accuracy

    Time frame: Acute (45, 180, 300 minutes post-dose)

    Average scores from the last five correctly completed trials from the corsi block-tapping task

  57. Corsi blocks accuracy

    Time frame: Chronic (57 days)

    Average scores from the last five correctly completed trials from the corsi block-tapping task

  58. Corsi blocks accuracy

    Time frame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)

    Average scores from the last five correctly completed trials from the corsi block-tapping task

  59. Choice reaction time accuracy

    Time frame: Acute (45, 180, 300 minutes post-dose)

    (%; 0-100; where higher is better)

  60. Choice reaction time accuracy

    Time frame: Chronic (57 days)

    (%; 0-100; where higher is better)

  61. Choice reaction time accuracy

    Time frame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)

    (%; 0-100; where higher is better)

  62. Choice reaction time reaction time

    Time frame: Acute (45, 180, 300 minutes post-dose)

    (ms; lower is better)

  63. Choice reaction time reaction time

    Time frame: Chronic (57 days)

    (ms; lower is better)

  64. Choice reaction time reaction time

    Time frame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)

    (ms; lower is better)

  65. Numeric working memory accuracy

    Time frame: Acute (45, 180, 300 minutes post-dose)

    (ms; lower is better)

  66. Numeric working memory accuracy

    Time frame: Chronic (57 days)

    (%; 0-100; where higher is better)

  67. Numeric working memory accuracy

    Time frame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)

    (%; 0-100; where higher is better)

  68. Numeric working memory reaction time

    Time frame: Acute (45, 180, 300 minutes post-dose)

    (ms; lower is better)

  69. Numeric working memory reaction time

    Time frame: Chronic (57 days)

    (ms; lower is better)

  70. Numeric working memory reaction time

    Time frame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)

    (ms; lower is better)

  71. Serial 3 subtractions total responses

    Time frame: Acute (45, 180, 300 minutes post-dose)

    number - calculated from the 3 cycles of the Cognitive Demand Battery; higher is better

  72. Serial 3 subtractions total responses

    Time frame: Chronic (57 days)

    number - calculated from the 3 cycles of the Cognitive Demand Battery; higher is better

  73. Serial 3 subtractions total responses

    Time frame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)

    number - calculated from the 3 cycles of the Cognitive Demand Battery; higher is better

  74. Serial 3 subtractions total error responses

    Time frame: Acute (45, 180, 300 minutes post-dose)

    number - calculated from the 3 cycles of the Cognitive Demand Battery; lower is better

  75. Serial 3 subtractions total error responses

    Time frame: Chronic (57 days)

    number - calculated from the 3 cycles of the Cognitive Demand Battery; lower is better

  76. Serial 3 subtractions total error responses

    Time frame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)

    number - calculated from the 3 cycles of the Cognitive Demand Battery; lower is better

  77. Serial 7 subtractions total responses

    Time frame: Acute (45, 180, 300 minutes post-dose)

    number - calculated from the 3 cycles of the Cognitive Demand Battery; higher is better

  78. Serial 7 subtractions total responses

    Time frame: Chronic (57 days)

    number - calculated from the 3 cycles of the Cognitive Demand Battery; higher is better

  79. Serial 7 subtractions total responses

    Time frame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)

    number - calculated from the 3 cycles of the Cognitive Demand Battery; higher is better

  80. Serial 7 subtractions total error responses

    Time frame: Acute (45, 180, 300 minutes post-dose)

    number - calculated from the 3 cycles of the Cognitive Demand Battery; lower is better

  81. Serial 7 subtractions total error responses

    Time frame: Chronic (57 days)

    number - calculated from the 3 cycles of the Cognitive Demand Battery; lower is better

  82. Serial 7 subtractions total error responses

    Time frame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)

    number - calculated from the 3 cycles of the Cognitive Demand Battery; lower is better

  83. Rapid visual information processing accuracy

    Time frame: Acute (45, 180, 300 minutes post-dose)

    (%) - calculated from the 3 cycles of the Cognitive Demand Battery (%; 0-100; where higher is better)

  84. Rapid visual information processing accuracy

    Time frame: Chronic (57 days)

    (%) - calculated from the 3 cycles of the Cognitive Demand Battery (%; 0-100; where higher is better)

  85. Rapid visual information processing accuracy

    Time frame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)

    (%) - calculated from the 3 cycles of the Cognitive Demand Battery (%; 0-100; where higher is better)

  86. Rapid visual information processing reaction time

    Time frame: Acute (45, 180, 300 minutes post-dose)

    (ms) - calculated from the 3 cycles of the Cognitive Demand Battery; lower is better

  87. Rapid visual information processing reaction time

    Time frame: Chronic (57 days)

    (ms) - calculated from the 3 cycles of the Cognitive Demand Battery; lower is better

  88. Rapid visual information processing reaction time

    Time frame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)

    (ms) - calculated from the 3 cycles of the Cognitive Demand Battery; lower is better

  89. Rapid visual information processing false alarms

    Time frame: Acute (45, 180, 300 minutes post-dose)

    number - calculated from the 3 cycles of the Cognitive Demand Battery; lower is better

  90. Rapid visual information processing false alarms

    Time frame: Chronic (57 days)

    number - calculated from the 3 cycles of the Cognitive Demand Battery; lower is better

  91. Rapid visual information processing false alarms

    Time frame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)

    number - calculated from the 3 cycles of the Cognitive Demand Battery; lower is better

  92. Mental fatigue

    Time frame: Acute (45, 180, 300 minutes post-dose)

    visual analogue scale (%) - calculated from the 3 cycles of the Cognitive Demand Battery (0-100; higher indicates more fatigue)

  93. Mental fatigue

    Time frame: Chronic (57 days)

    visual analogue scale (%) - calculated from the 3 cycles of the Cognitive Demand Battery (0-100; higher indicates more fatigue)

  94. Mental fatigue

    Time frame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)

    visual analogue scale (%) - calculated from the 3 cycles of the Cognitive Demand Battery (0-100; higher indicates more fatigue)

  95. Subjective mood - Alert

    Time frame: Acute (45, 180, 300 minutes post-dose)

    derived from Bond Lader visual analogue scales (0-100; higher is more alert)

  96. Subjective mood - Alert

    Time frame: Chronic (57 days)

    derived from Bond Lader visual analogue scales (0-100; higher is more alert)

  97. Subjective mood - Alert

    Time frame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)

    derived from Bond Lader visual analogue scales (0-100; higher is more alert)

  98. Subjective mood - Content (visual analogue scale)

    Time frame: Acute (45, 180, 300 minutes post-dose)

    derived from Bond Lader visual analogue scales (0-100 higher is more content)

  99. Subjective mood - Content

    Time frame: Chronic (57 days)

    derived from Bond Lader visual analogue scales(0-100 higher is more content)

  100. Subjective mood - Content

    Time frame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)

    derived from Bond Lader visual analogue scales(0-100 higher is more content)

  101. Subjective mood - Calm

    Time frame: Acute (45, 180, 300 minutes post-dose)

    derived from Bond Lader visual analogue scales (0-100 higher is more calm)

  102. Subjective mood - Calm

    Time frame: Chronic (57 days)

    derived from Bond Lader visual analogue scale (0-100 higher is more calm)

  103. Subjective mood - Calm (Bond Lader visual analogue scale)

    Time frame: Superimposed chronic (57 days plus 45, 180, 300 minutes post-dose)

    derived from Bond Lader visual analogue scale (0-100 higher is more calm)

  104. Cerebral blood flow during performance of cognitive tasks

    Time frame: Acute (120, 150 minutes post-dose)

    Measured (in umol) using quantitative near infrared spectroscopy (higher indicates increased blood volume)

  105. Cerebral blood flow during performance of cognitive tasks

    Time frame: Superimposed chronic (57 days plus 120, 150 minutes post-dose)

    Measured (in umol) using quantitative near infrared spectroscopy (higher indicates increased blood volume)

  106. Cerebral blood flow at rest

    Time frame: Acute (120, 150 minutes post-dose)

    Measured (in umol) using quantitative near infrared spectroscopy (higher indicates increased blood volume)

  107. Cerebral blood flow at rest

    Time frame: Chronic (57 days)

    Measured (in umol) using quantitative near infrared spectroscopy (higher indicates increased blood volume)

  108. Cerebral blood flow at rest

    Time frame: Superimposed chronic (57 days plus 120, 150 minutes post-dose)

    Measured (in umol) using quantitative near infrared spectroscopy (higher indicates increased blood volume)

Sponsors and collaborators

Lead sponsor

Northumbria University

Other

Collaborators

  • Mibelle AG

Registry information

Official study 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

Important dates

Study start
2018
Primary completion
2018
Study completion
2018
First posted
Sep 17, 2018
Registry last updated
Jan 24, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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