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Trial record 8 of 25769 for:    Change | Recruiting, Not yet recruiting, Available Studies

Intermittent Energy Restriction and Chewing on Neural Stem Cell Ageing and Adult Hippocampal Neurogenesis Associated Cognition (ChANgE)

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ClinicalTrials.gov Identifier: NCT03457870
Recruitment Status : Not yet recruiting
First Posted : March 8, 2018
Last Update Posted : March 8, 2018
Sponsor:
Collaborators:
Medical Research Council
Mars, Incorporated
Information provided by (Responsible Party):
King's College London

Brief Summary:
Extended bouts of periodic mastication and intermittent energy restriction (IER) may improve cognitive performance in the context of adult hippocampal neurogenesis in an ageing population. A randomised controlled parallel design trial will determine the impact of a 3 month IER diet (2 consecutive days of very low calorie diet and 5 days of normal eating) and a mastication intervention (1 piece of gum chewed for 10 minutes 3 times a day) in comparison to a control on neurogenesis-associated cognitive measures and circulating levels of the anti-ageing protein Klotho.

Condition or disease Intervention/treatment Phase
Aging Cognitive Decline Behavioral: Intermittent Energy Restriction Behavioral: Chewing Behavioral: Chewing + Intermittent Energy Restriction Not Applicable

Detailed Description:

Nutrition and human health are strongly related. Altering overabundance through fasting/calorie-restricted diets has profound effects on homeostasis, tissue regeneration, and cancer. Tissue stem cells respond to the physiological changes that occur during fasting through dynamic shifts in their metabolism. Restricting energy intake in mice or introducing mutations in nutrient-sensing pathways can extend lifespans by as much as 50%. Post-mortems reveal that tumours, heart problems, neurodegeneration and metabolic disease are generally reduced/delayed in long-lived mice. Therefore, extending lifespan by energy restriction (ER) also seems to increase 'healthspan', the time lived without chronic age-related conditions. These insights have hardly made a dent in human medicine. Molecular and cellular insights should be established in humans to validate interventions such as ER to delay ageing and associated conditions e.g. cognitive decline (Murphy et al., 2014).

Stem cells from the central nervous system also respond to ER. Recently, the Thuret lab have found that ER, in the absence of malnutrition, promotes hippocampal stem cells to proliferate and differentiate into new-born neurons. Because these new postnatal hippocampal neurons have been shown to play a role in cognition, ER also promoted enhanced cognition in rodents (Zainuddin et al., 2012; de Lucia et al., 2017; Thuret et al., 2012). This phenomenon of neurogenesis, the process by which new neurons are generated from neural stem cells, is also occurring in humans (Spalding et al., 2013). It is a tightly regulated process occurring in the mammalian hippocampus which is an environmentally responsive brain structure known to regulate learning, memory and mood. Proposed functions of adult hippocampal neurogenesis (AHN). include enhancing recognition memory, the ability to recognise previously encountered stimuli, and pattern separation, the ability to differentially encode small changes in similar inputs (Clelland et alk., 2009; Sahay et al., 2011). It has been posited that calorie restriction may increase neurogenesis as a "cellular relic" of intermittent feeding patterns during evolution as a response to alternating periods of famine and abundant food (Murphy & Thuret, 2015). Human trials have found significant improvements in verbal recognition memory after 30% reduction in calorie intake (Witte et al., 2009). Also, intermittent fasting in humans has been associated with significant increases in brain activation volume in areas involved in brain function control and plasticity(Belaïch et al., 2016). Food texture and mastication have also been implicated in AHN and cognitive ability (Smith et al., 2016). Decreased mastication due to the removal of molars and edentulism in both humans and animals have a negative impact on AHN and associated cognition. Human populations, in particular, have shown a close association between masticatory function, cognitive status and age-related neurodegeneration in the elderly (Miura et al., 2003). The exact mechanism by which mastication affects cognition is unknown.

Research question: In older, overweight participants does IER and/or extended periods of mastication enhance performance inhippocampus-dependent memory tasks and increase anti-ageing marker Klotho?

Objectives:

  1. A randomised controlled parallel-design trial will determine the impact of an IER diet (2 consecutive days of a very low calorie diet, 5 days of normal healthy eating for 3 months) and/or extended periods of mastication (10 minutes 3 times a day for 3 months) compared to a control group (continued habitual eating behaviour, dietary patterns) on primary outcome variables (MST and Klotho) in older, healthy participants with overweight or class I obesity.
  2. To assess the impact of an IER diet and extended periods of mastication on secondary outcomes variables including body composition, mood and sleep.
  3. To explore whether extended periods of mastication can be utilised as a weight loss/fasting aid.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 132 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Investigating the Impact of Intermittent Energy Restriction and Chewing on Neural Stem Cell Ageing and Adult Hippocampal Neurogenesis: The ChANgE Study
Estimated Study Start Date : March 2018
Estimated Primary Completion Date : March 2019
Estimated Study Completion Date : March 2019

Arm Intervention/treatment
Experimental: Intermittent Energy Restriction
Dietary intervention: Intermittent energy restriction
Behavioral: Intermittent Energy Restriction
Dietary advice to follow a 5:2 diet.

Experimental: Chewing
Mastication intervention: chewing
Behavioral: Chewing
Asked to chew 1 piece of gum for 10 minutes 3 times a day.

Experimental: Chewing + Intermittent Energy Restriction
Dietary and mastication intervention: Intermittent energy restriction and chewing
Behavioral: Chewing + Intermittent Energy Restriction
Dietary advice to follow a 5:2 diet. Asked to chew 1 piece of gum for 10 minutes 3 times a day.

No Intervention: Control
No intervention: Control



Primary Outcome Measures :
  1. Serum Klotho concentration [ Time Frame: Baseline ]
    Anti-ageing longevity protein

  2. Serum Klotho concentration [ Time Frame: Day 42 ]
    Anti-ageing longevity protein

  3. Serum Klotho concentration [ Time Frame: Day 84 ]
    Anti-ageing longevity protein

  4. Mnemonic Similarity Task [ Time Frame: Baseline ]
    Neurogenesis-associated cognition

  5. Mnemonic Similarity Task [ Time Frame: Day 42 ]
    Neurogenesis-associated cognition


Secondary Outcome Measures :
  1. Body weight [ Time Frame: Baseline ]
  2. Body weight [ Time Frame: Day 42 ]
  3. Body weight [ Time Frame: Day 84 ]
  4. Body fat percentage [ Time Frame: Baseline ]
  5. Body fat percentage [ Time Frame: Day 42 ]
  6. Body fat percentage [ Time Frame: Day 84 ]
  7. Body Mass Index [ Time Frame: Baseline ]
  8. Body Mass Index [ Time Frame: Day 42 ]
  9. Body Mass Index [ Time Frame: Day 84 ]
  10. Waist circumference [ Time Frame: Baseline ]
  11. Waist circumference [ Time Frame: Day 42 ]
  12. Waist circumference [ Time Frame: Day 84 ]
  13. Hip circumference [ Time Frame: Baseline ]
  14. Hip circumference [ Time Frame: Day 42 ]
  15. Hip circumference [ Time Frame: Day 84 ]
  16. Patient Health Questionnaire [ Time Frame: Baseline ]
    Questionnaire

  17. Patient Health Questionnaire [ Time Frame: Day 42 ]
    Questionnaire

  18. Patient Health Questionnaire [ Time Frame: Day 84 ]
    Questionnaire

  19. Zung Self-Rating Anxiety Scale [ Time Frame: Baseline ]
    Questionnaire - Scale can be scored from 20 (normal) to 80 (extreme anxiety levels). The total score is reported.

  20. Zung Self-Rating Anxiety Scale [ Time Frame: Day 42 ]
    Questionnaire

  21. Zung Self-Rating Anxiety Scale [ Time Frame: Day 84 ]
    Questionnaire

  22. Pittsburgh Sleep Quality Index [ Time Frame: Baseline ]
    Questionnaire

  23. Pittsburgh Sleep Quality Index [ Time Frame: Day 42 ]
    Questionnaire

  24. Pittsburgh Sleep Quality Index [ Time Frame: Day 84 ]
    Questionnaire

  25. Plasma glucose concentration [ Time Frame: Baseline ]
    Fasting

  26. Plasma glucose concentration [ Time Frame: Day 42 ]
    Fasting

  27. Plasma glucose concentration [ Time Frame: Day 84 ]
    Fasting

  28. Cholesterol [ Time Frame: Baseline ]
    Fasting

  29. Cholesterol [ Time Frame: Day 42 ]
    Fasting

  30. Cholesterol [ Time Frame: Day 84 ]
    Fasting

  31. Triglycerides [ Time Frame: Baseline ]
    Fasting

  32. Triglycerides [ Time Frame: Day 42 ]
    Fasting

  33. Triglycerides [ Time Frame: Day 84 ]
    Fasting

  34. High Density Lipoprotein [ Time Frame: Baseline ]
    Fasting

  35. High Density Lipoprotein [ Time Frame: Day 42 ]
    Fasting

  36. High Density Lipoprotein [ Time Frame: Day 84 ]
    Fasting

  37. Low Density Lipoprotein [ Time Frame: Baseline ]
    Fasting

  38. Low Density Lipoprotein [ Time Frame: Day 42 ]
    Fasting

  39. Low Density Lipoprotein [ Time Frame: Day 84 ]
    Fasting

  40. Total/HDL Cholesterol Ratio [ Time Frame: Baseline ]
    Fasting

  41. Total/HDL Cholesterol Ratio [ Time Frame: Day 42 ]
    Fasting

  42. Total/HDL Cholesterol Ratio [ Time Frame: Day 84 ]
    Fasting

  43. Plasma adiponectin concentration [ Time Frame: Baseline ]
    Fasting

  44. Plasma adiponectin concentration [ Time Frame: Day 42 ]
    Fasting

  45. Plasma adiponectin concentration [ Time Frame: Day 84 ]
    Fasting

  46. Plasma leptin concentration [ Time Frame: Baseline ]
    Fasting

  47. Plasma leptin concentration [ Time Frame: Day 42 ]
    Fasting

  48. Plasma leptin concentration [ Time Frame: Day 84 ]
    Fasting

  49. Plasma beta-hydroxybutrate concentration [ Time Frame: Baseline ]
    Fasting

  50. Plasma beta-hydroxybutrate concentration [ Time Frame: Day 42 ]
    Fasting

  51. Plasma beta-hydroxybutrate concentration [ Time Frame: Day 84 ]
    Fasting

  52. Plasma total cholesterol concentration [ Time Frame: Baseline ]
    Fasting

  53. Plasma total cholesterol concentration [ Time Frame: Day 42 ]
    Fasting

  54. Plasma total cholesterol concentration [ Time Frame: Day 84 ]
    Fasting

  55. Plasma low density lipoprotein (LDL) cholesterol concentration [ Time Frame: Baseline ]
    Fasting

  56. Plasma LDL cholesterol concentration [ Time Frame: Day 42 ]
    Fasting

  57. Plasma LDL cholesterol concentration [ Time Frame: Day 84 ]
    Fasting

  58. Plasma high density lipoprotein (HDL) cholesterol concentration [ Time Frame: Baseline ]
    Fasting

  59. Plasma HDL cholesterol concentration [ Time Frame: Day 42 ]
    Fasting

  60. Plasma HDL cholesterol concentration [ Time Frame: Day 84 ]
    Fasting

  61. Plasma triglyceride concentration [ Time Frame: Baseline ]
    Fasting

  62. Plasma triglyceride concentration [ Time Frame: Day 42 ]
    Fasting

  63. Plasma triglyceride concentration [ Time Frame: Day 84 ]
    Fasting

  64. Plasma total cholesterol:HDL cholesterol ratio [ Time Frame: Baseline ]
    Fasting

  65. Plasma total cholesterol:HDL cholesterol ratio [ Time Frame: Day 42 ]
    Fasting

  66. Plasma total cholesterol:HDL cholesterol ratio [ Time Frame: Day 84 ]
    Fasting


Other Outcome Measures:
  1. Adverse events [ Time Frame: Baseline until endpoint: Day 84 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   60 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Male and female subjects.
  • 60+ years of age at the time of consent.
  • BMI 25-35.

Exclusion Criteria:

  • Subject is unable to understand the participant information sheet.
  • Subject is unable to understand and/or completely perform the cognitive testing.
  • Chews more than 3 sticks of gum per month, including nicotine replacement gum.
  • Unable to provide written informed consent.
  • Impaired vision that is not corrected.
  • Does not agree to maintain their habitual exercise routine.
  • Is not in general good health on the basis of medical history.
  • Unwilling to chew gum for 3 times a day for 12 weeks.
  • Unwilling to maintain an intermittent fasting diet regime.
  • Unwilling to have blood taken.
  • History of or are currently diagnosed with a significant psychiatric disorder (e.g. schizophrenia, anxiety, PTSD).
  • Subject has any neurological disorder that could produce cognitive deterioration (e.g. Alzheimer's disease, Parkinson's disease, stroke).
  • History of traumatic brain injury, stroke or any other medical conditions causing cognitive impairment.
  • Has uncontrolled epilepsy or is prone to fainting.
  • Participated in a weight management drug trial in previous 3 months.
  • Has undergone bariatric surgery.
  • Known or suspected of alcohol abuse defined as >14 drinks per week (1 drink = 1 pint of beer, 1 large glass of wine or 50ml spirit).
  • Gastrointestinal or liver disease.
  • Subject has a sleep disorder or an occupation where sleep during the overnight hours is irregular.
  • Subjects taking the following prescription medications: Donepezil (Aricept), Galantamine (Reminyl), Rivastigmine (Exelon), Tacrine (Cognex), Bethanechol (Urecholine), Memantine (Namenda) Selegiline (Eldepryl) or any other medication for cognitive impairment.
  • Subject has a known sensitivity to the study product.
  • Individual has a condition the chief investigator believes would interfere with his or her ability to provide informed consent, comply with the study protocol, might confound the interpretation of study results or put the subject at undue risk.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03457870


Contacts
Contact: Sandrine Thuret, PhD 02078485405 sandrine.1.thuret@kcl.ac.uk
Contact: Curie Kim, MSc 02078484345 change@kcl.ac.uk

Locations
United Kingdom
Diabetes & Nutritional Sciences Division, King's College London, Franklin-Wilkins Building, 150 Stamford St Not yet recruiting
London, England, United Kingdom, SE1 9NH
Contact: Wendy L Hall, PhD    02078484197    wendy.hall@kcl.ac.uk   
Contact: Curie Kim, MSc    02078484345    curie.kim@kcl.ac.uk   
Sponsors and Collaborators
King's College London
Medical Research Council
Mars, Incorporated
Investigators
Principal Investigator: Sandrine Thuret, PhD King's College London
Principal Investigator: Wendy L Hall, PhD King's College London

Publications:
Responsible Party: King's College London
ClinicalTrials.gov Identifier: NCT03457870     History of Changes
Other Study ID Numbers: Change 2018
First Posted: March 8, 2018    Key Record Dates
Last Update Posted: March 8, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by King's College London:
Intermittent fasting
Adult hippocampal neurogenesis
Mastication
Pattern separation
Recognition memory
Klotho

Additional relevant MeSH terms:
Cognitive Dysfunction
Cognition Disorders
Neurocognitive Disorders
Mental Disorders