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A Phase II Study to Assess the Safety, Tolerability and Efficacy of Xanamem™ in Subjects With Mild Dementia Due to AD (XanADu) (XanADu)

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ClinicalTrials.gov Identifier: NCT02727699
Recruitment Status : Recruiting
First Posted : April 5, 2016
Last Update Posted : May 31, 2018
Sponsor:
Collaborator:
ICON Clinical Research
Information provided by (Responsible Party):
Actinogen Medical

Brief Summary:
This XanADu Phase II study in mild Alzheimer's Disease (AD) is to assess the safety, tolerability and efficacy of Xanamem™ in subjects with mild dementia due to Alzheimer's Disease. Subjects will be randomized to receive either 10mg once daily Xanamem™ or Placebo at a 1:1 ratio in a double-blinded fashion.

Condition or disease Intervention/treatment Phase
Dementia Drug: Xanamem™ Drug: Placebo (for Xanamem™) Phase 2

Detailed Description:

This is a Phase II, randomised, multi-centre, double-blind, placebo-controlled proof-of-concept study to assess the safety, tolerability and efficacy of oral Xanamem™ once daily in adult subjects with mild dementia due to AD.

Based on Xanamem™'s mode of action on hippocampal function, amnestic symptoms may respond best, thus favouring the inclusion of mild dementia due to AD, with given evidence of disease progression. Subjects will be treated in a double-blind fashion, where both the investigators and subjects will be unaware of the treatment assignments, to minimise any subjective or unrecognised bias carried by the investigators and subjects. Placebo will be used as the comparator in this study. In this study, Xanamem™ will be administered in conjunction with current standard therapy.

It is planned to randomise approximately 174 subjects at approximately 20 study sites in three countries (Australia, United Kingdom, and United States), with the aim to enrol 7 to 10 subjects at each study site. Subject enrolment will be competitive but a cap of 20 subjects per study site is to be established to avoid any site effects. In case the sample composition at one study site is creating concerns, an enrolment stop can also occur at fewer than 20 subjects.

The data safety monitoring board (DSMB) will periodically meet for the review of accumulating safety study data and will also be involved in the interim analysis.

At the Baseline visit (Week 0), eligible subjects will be randomised on a 1:1 ratio to receive either Xanamem™ administered orally QD (treatment group) or matching placebo (placebo group). Subjects will return to the study site for visits at Week 4 and Week 8, End of Treatment (Week 12) and Follow-up (4 weeks post last dose of study drug) visits, at which study assessments will be performed.

Ad hoc telephone contact may also occur at any other time-point throughout the study, if deemed necessary by the investigator/study nurse, or if the subject wishes to report an AE.

Subjects will be interviewed and examined at the study site at each visit, and will complete a variety of questionnaires and routine safety evaluations.

Optional PD sampling will be performed at specific visits. Subjects who do not provide consent for this optional sub-study will still be eligible for the main study.

The overall study duration for an individual subject will be 17 to 20 weeks, including a screening period of one to 4 weeks, a double-blind treatment period of 12 weeks, and a follow-up period of 4 weeks. The total duration of the study is expected to be 2 years.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 174 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: XanADu: A Phase II, Double-Blind, 12-Week, Randomised, Placebo-Controlled Study to Assess the Safety, Tolerability and Efficacy of Xanamem™ in Subjects With Mild Dementia Due to Alzheimer's Disease (AD)
Actual Study Start Date : March 23, 2017
Estimated Primary Completion Date : January 2019
Estimated Study Completion Date : March 2019


Arm Intervention/treatment
Experimental: Xanamem™
Oral Xanamem™ capsules 10mg, to be administered once daily
Drug: Xanamem™
Xanamem™ is formulated in green and cream coloured size 3, Coni-Snap shaped gelatin capsules as an excipient blend at a dose of 10mg. It contains active pharmaceutical ingredient of UE2343
Other Name: UE2343

Placebo Comparator: Placebo
Matching placebo which is identical in appearance to the test product except that it contains no active ingredient, to be administered once daily
Drug: Placebo (for Xanamem™)
Excipient blend capsules manufactured to mimic Xanamem™ capsules
Other Name: Placebo




Primary Outcome Measures :
  1. ADAS-Cog v14 [ Time Frame: Baseline, Week 12 ]
    Change in Alzheimer's Disease Assessment Scales - Cognitive Subscale Score, version 14 (ADAS-Cog v14)

  2. AD COMposite Scores [ Time Frame: Baseline, Week 12 ]
    Change in AD COMposite Scores (ADCOMs, composite data derived from Alzheimer's Disease Assessment Scales - Cognitive Subscale Version 14 [ADAS-Cog v14], Clinical Dementia Rating Scale - Sum of Boxes [CDR-SOB], and Mini-Mental Status Examination [MMSE])


Secondary Outcome Measures :
  1. RAVLT [ Time Frame: Baseline, Week 12 ]
    Change in Rey Auditory Verbal Learning Test (RAVLT)

  2. CDR-SOB [ Time Frame: Screening, Baseline, Week 12 ]
    Change in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SOB) and Global (CDR Global)

  3. MMSE [ Time Frame: Screening, Baseline, Week 12 ]
    Change in Mini-Mental Status Examination (MMSE)

  4. NPI [ Time Frame: Baseline, Week 12 ]
    Change in Neuropsychiatric Inventory (NPI)

  5. NTB - Executive Domain [ Time Frame: Baseline, Week 12 ]
    Change in Neuropsychological Test Batteries (NTB) - Executive Domain (COWAT and CFT)


Other Outcome Measures:
  1. Clinical Safety Laboratory Values [ Time Frame: Screening, Baseline, Week 4, Week 8, Week 12, Week 16 ]
    Change in Clinical Safety Laboratory Values (biochemistry, haematology, urine examination)

  2. AEs [ Time Frame: Screening, Baseline, Week 4, Week 8, Week 12, Week 16, Ad Hoc ]
    Incidence of Adverse Events (AEs)

  3. ECG [ Time Frame: Screening, Baseline, Week 4, Week 8, Week 12, Week 16 ]
    Change in Electrocardiogram (ECG) Values

  4. CSSRS [ Time Frame: Screening, Week 4, Week 8, Week 12, Week 16 ]
    Change in Scores of Columbia Suicide Severity Rating Scale (CSSRS)

  5. Metabolic Function [ Time Frame: Baseline, Week 12 ]
    Change in Metabolic Function Test Results of Lipids, Glucose, Haemoglobin A1c (HbA1c)

  6. Vital Signs [ Time Frame: Screening, Baseline, Week 4, Week 8, Week 12, Week 16, Unscheduled Safety Visit ]
    Change in Vital Signs (including Heart Rate, Blood Pressure, Body Weight, BMI)

  7. NFM [ Time Frame: Screening, Baseline, Week 4, Week 8, Week 12, Week 16 ]
    Change in Nerve Function Monitoring (NFM)

  8. NTSS-6 [ Time Frame: Screening, Baseline, Week 4, Week 8, Week 12, Week 16, Ad Hoc and Unscheduled Safety Visit ]
    Change in Neuropathy Total Symptom Score (NTSS-6)

  9. PK [ Time Frame: Baseline, Week 4, Week 8, Week 12 and Unscheduled Safety Visit ]
    Change in Pharmacokinetics (PK)

  10. Optional PD Assessment - Changes in Pharmacodynamic (PD) measures of adrenocorticotropic hormone (ACTH) [ Time Frame: Baseline, Week 4, Week 8, Week 12, Week 16 ]
    This assessment will be carried out on approximately 50 subjects who consented to this optional test. PD sample will be collected at pre-dose at each required visit

  11. Optional PD Assessment - Changes in Pharmacodynamic (PD) measures of dehydroepiandrosterone Sulfate (DHEAS) [ Time Frame: Baseline, Week 4, Week 8, Week 12, Week 16 ]
    This assessment will be carried out on approximately 50 subjects who consented to this optional test. PD sample will be collected at pre-dose at each required visit

  12. Optional PD Assessment - Changes in Pharmacodynamic (PD) measures of Androstenedione [ Time Frame: Baseline, Week 4, Week 8, Week 12, Week 16 ]
    This assessment will be carried out on approximately 50 subjects who consented to this optional test. PD sample will be collected at pre-dose at each required visit

  13. Optional PD Assessment - Changes in Pharmacodynamic (PD) measures of Testosterone [ Time Frame: Baseline, Week 4, Week 8, Week 12, Week 16 ]
    This assessment will be carried out on approximately 50 subjects who consented to this optional test. PD sample will be collected at pre-dose at each required visit

  14. Pregnancy Test [ Time Frame: Screening, Baseline, Week 4, Week 8, Week 12, Week 16 ]
    Women of Childbearing (WOCB) potential only. Serum pregnancy test at Screening and a urine pregnancy test at all subsequent clinic visits.



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:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Males and females aged 50 years or older at the time of informed consent.
  2. Female Subjects:

    1. Post menopausal women, defined as no menses for 12 months without an alternative medical cause. If there is any concern about the menopausal status of a prospective female subject, a follicle stimulating hormone test (FSH) should be requested to confirm post-menopausal status. Post menopausal women confirmed by FSH level > 40 mIU/mL, will be confirmed by central laboratory.
    2. Women of childbearing potential (WOCBP) must have a negative pregnancy test at Screening and Baseline, and be willing to use highly effective methods of contraception from the Screening visit until 3 months after last dose of study drug. If re-test is required, a local urine pregnancy test will be performed at Baseline to determine if the subject can continue to randomisation.
    3. Are permanently sterile or have had a hysterectomy, bilateral salpingectomy or bilateral oophorectomy.
    4. Women must not be breastfeeding.
  3. Male Subjects:

    1. Who are sexually active, fertile men must use highly effective methods of contraception from Day 1 until 3 months after last dose of study drug if their partners are WOBC.
    2. Who are permanently sterile or have had bilateral orchiectomy.
  4. Diagnosis of mild dementia due to Alzheimer's disease (AD) with increased level of certainty (provided by evidence of clinical deterioration within the 6 months preceding Screening, as assessed by the investigator) as determined by the National Institute of Ageing (NIA) and the Alzheimer's Association (AA) workgroup.
  5. Mild dementia due to probable AD with MMSE 20 to 26 (inclusive).
  6. Clinical Dementia Rating Scale (CDR) Global Score of 0.5 to 1.0.
  7. A brain magnetic resonance imaging (MRI) or computed tomography (CT) scan in the 12 months preceding Screening that in the investigator's opinion is consistent with AD as the principle aetiology of the dementia with no other clinically significant abnormality, e.g. another principle underlying aetiology of the subject's dementia, or a lesion which could affect cognition e.g. a brain tumour or large stroke.
  8. On stable dose of acetylcholinesterase (AChEI) and/or memantine (at least 3 months prior to Screening) OR treatment-naïve. Initiating AChEIs or memantine during the study will not be permitted.
  9. Apart from a clinical diagnosis of mild dementia due to AD, the subject must be in good health as determined by the investigator, based on medical history and screening assessments.
  10. Has a consenting study partner who, in the investigator's judgement, has frequent and sufficient contact with the subject to be able to provide accurate information as to the subject's cognitive and functional abilities. The study partner must be available to provide information to the investigator and study site staff about the subject and agrees to attend all study site visits in person for scale completion. A study partner should be available for the duration of the study. The measure of adequate availability will be at the investigator's discretion.
  11. Must be willing and able to comply with the requirements of the protocol and must be available to complete the study.
  12. Must satisfy a medical examiner about their fitness to participate in the study.
  13. Must provide written informed consent to participate in the study.

Exclusion Criteria:

  1. Clinically significant abnormalities in vital signs (blood pressure, heart rate, respiration rate and oral temperature), as determined by the investigator.
  2. Clinically significant abnormal haematology, biochemistry and urine examination values, specifically abnormal liver and renal function and Vitamin B12 levels below lower threshold since these parameters may impact cognitive function, as determined by the investigator.
  3. Has had a significant systematic illness or infection within the past 4 weeks prior to randomisation, as determined by the investigator.
  4. Clinically significant neurological disease other than AD, such as (but not limited to) Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumour, progressive supranuclear palsy, seizure disorder, subdural haematoma, multiple sclerosis or a history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities.
  5. Subjects with clinical evidence of peripheral neuropathy or historical evidence of clinically significant nerve conduction abnormalities.
  6. Has had a stroke within the year prior to randomisation, as determined by the investigator.
  7. Has a lifetime diagnosis of a major psychiatric disorder (other than dementia), based on the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria. This includes but is not limited to schizophrenia, schizoaffective disorder, bipolar affective disorder, alcohol dependence syndrome or major depressive disorder.
  8. Has a history of disease directly related to the hypothalamus, the pituitary and/or the adrenal glands which affect the hypothalamic-pituitary-adrenal axis function.
  9. Has uncontrolled clinical conditions relating to glucose and lipid metabolism.
  10. Clinically significant electrocardiogram (ECG) abnormalities, including QTc interval > 450 ms, following ECG tracings at Screening.
  11. Use of any prohibited medication as detailed in the study protocol.
  12. Participation in another clinical study of an investigational drug or device whereby the last investigational drug/device administration is within 60 days of Screening.
  13. Inability to communicate well with the investigator (i.e. language problem, non-fluent English [as scales will be provided in English only], poor mental development or impaired cerebral function).
  14. Subject will undergo the tests, ADAS-Cog v14, CDR-SOB, MMSE, NTB (executive domain) and RAVLT at the indicated time-points to avoid uncontrolled learning effects. Subjects who need to perform these tests externally to and in parallel with this study will be excluded.
  15. Subject has ingested any food or drink containing grapefruit, Seville oranges, star fruit or derived products (e.g. fruit juice), for at least 3 days prior to the first administration of study drug.

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): NCT02727699


Contacts
Contact: Vincent Ruffles +61 2 8964 7401 Vincent.Ruffles@actinogen.com.au
Contact: Tamara Miller +61 2 8964 7401 Tamara.Miller@actinogen.com.au

Locations
United States, Arizona
Tucson Neuroscience Research, LLC Recruiting
Tucson, Arizona, United States, 85710
Contact: CarliAnn Golden    520-829-7502    cgolden@tucsonneuroscience.com   
Contact    +1 (520) 225-0382      
Principal Investigator: Diana Benenati, MD         
United States, California
National Research Institute Recruiting
Los Angeles, California, United States, 90057
Contact: Kyle Bullock    818-572-0186    kyle.bullock@nritrials.com   
Contact: Sandee Orozco    +1 (818) 532- 6880    sandee.orozco@nritrials.com   
Principal Investigator: Juan Pablos Frias, Dr         
PCND Neuroscience Research Institute Recruiting
Poway, California, United States, 92064
Contact: Jane Tran    858-674-1289    jtran@pcndneurology.com   
Contact: Meg Maeda, MD    +1 (858) 674-1289    mmaeda@pcndneurology.com   
Principal Investigator: Gilbert J Ho, MD         
Northern California Research Withdrawn
Sacramento, California, United States, 95821
United States, Florida
Research Alliance Inc. Recruiting
Clearwater, Florida, United States, 33756
Contact: Jodi Swierzewski    727-631-0779    jodi@researchalliance.net   
Contact: Frank Persechino    +1 (727) 631-0779    frank@researchalliance.net   
Principal Investigator: Diana Pollock, MD         
The Neurology Research Group, LLC Recruiting
Miami, Florida, United States, 33186
Contact: Savannah Rodriguez    305-596-2080    srodriguez@fcneurology.net   
Contact    +1 (305) 306-6207      
Principal Investigator: Brad Herskowitz, MD         
Compass Research LLC Recruiting
Orlando, Florida, United States, 32806
Contact: Taylor Rice    407-210-1309    trice@compassresearch.com   
Contact: Stephanie Armendariz    +1 (407) 404-7703    Stephanie.Armendariz@compass.bioclinica.com   
Sub-Investigator: Craig Curtis, MD         
Principal Investigator: Ira Goodman, MD         
IMIC, Inc. Active, not recruiting
Palmetto Bay, Florida, United States, 33157
United States, Georgia
Atlanta Center for Medical Research Recruiting
Atlanta, Georgia, United States, 30331
Contact: Carol Hannasch    404-881-5800    channasch@acmr.org   
Contact: Alexis K Melson    +1 (404) 881-5800    amelson@acmr.org   
Principal Investigator: Robert A Riesenberg, MD         
NeuroStudies.Net, LLC Recruiting
Decatur, Georgia, United States, 30033
Contact: Nino Valishvili    404-475-0552    NValishvili@neurostudies.net   
Contact: Jennifer Cavin    +1 (404) 475-0552    jcavin@neurostudies.net   
Principal Investigator: Marshall Nash, MD         
United States, New Jersey
The NeuroCognitive Institute Recruiting
Mount Arlington, New Jersey, United States, 07856
Contact: Charlene Carlo, MD    973-398-2900    cc@neuroci.com   
Contact: Estela Soniel    +1 (973) 299-9444    es@neuroci.com   
Principal Investigator: Gerald Tramontano, MD         
United States, New York
Richmond Behavioral Associates Recruiting
Staten Island, New York, United States, 10312
Contact: Deborah Arias    718-317-5522 ext 307    arias@rbany.com   
Contact: Nicholas Volpe    +1 (718) 317-5522    volpe@rbany.com   
Principal Investigator: Mark DiBuono, MD         
United States, North Carolina
PMG Research of Rocky Mount, LLC Recruiting
Rocky Mount, North Carolina, United States, 27804
Contact: Danielle Oliver    252-937-0484    Danielle.oliver@pmg-research.com   
Contact: Albrie Tucker    +1 (252) 937-0484    Albrie.Tucker@pmg-research.com   
Principal Investigator: Aurora K Pajeau, MD         
United States, Pennsylvania
The Clinical Trial Center Recruiting
Jenkintown, Pennsylvania, United States, 19046
Contact: Alketa Dobi    215-884-1700    alketa@theclinicaltrialcenter.com   
Contact: Cheryl Herbert    +1 (215) 884-1700    cheryl@theclinicaltrialcenter.com   
Principal Investigator: Marvin Kalafer, MD         
Australia, New South Wales
St Vincent's Hospital Sydney Recruiting
Darlinghurst, New South Wales, Australia, 2010
Contact: Marko Garcia    +61 2 8382 4977    marko.garcia@svha.org.au   
Contact: Joshua Carey    +61 2 8382 4986    Joshua.Carey@svha.org.au   
Principal Investigator: Bruce Brew, Prof         
KaRa Institute of Neurological Diseases Recruiting
Macquarie Park, New South Wales, Australia, 2113
Contact: Kathryn Goozee    +61 2 8960 7788    kathryn.goozee@karaminds.com.au   
Contact: Candice Man Yan    +61 2 8960 7788    Candice.ManYan@anglicare.org.au   
Principal Investigator: Rosalyn Lai, Dr         
Sub-Investigator: Kathryn Goozee         
Central Coast Neurosciences Research Recruiting
Tumbi Umbi, New South Wales, Australia, 2261
Contact: Michelle Anderson    +61 2 4324 9811    Michelle@neurosciences.com.au   
Contact: Angela Clair    +61 2 432 49811    Angela@neurosciences.com.au   
Principal Investigator: Jonathan Sturm, MD         
Sub-Investigator: Denis Crimmins, Asst Prof         
Australia, Victoria
Medical & Cognitive Research Unit, Heidelberg Repatriation Hospital - Austin Health Recruiting
Heidelberg West, Victoria, Australia, 3081
Contact: Pascal Bisscheroux    +61 3 9496 4238    Pascal.BISSCHEROUX@austin.org.au   
Contact: Beatriz Webb    +61 419 137 035    beatriz.webb@austin.org.au   
Principal Investigator: Henry Zeimer, Dr         
Sub-Investigator: Michael Woodward, Assoc Prof         
Royal Melbourne Hospital Withdrawn
Parkville, Victoria, Australia, 3050
Australia, Western Australia
Australian Alzheimer's Research Foundation Recruiting
Nedlands, Western Australia, Australia, 6009
Contact: +61 8 9389 6433 Mather, MD    08 6457 0253    info@alzheimers.com.au   
Contact: Sarah Ho    +61 8 9389 6433    sarah.ho@alzheimers.com.au   
Principal Investigator: Roger Clarnette, Assoc Prof         
United Kingdom
The Research Institute for the Care of Older People Recruiting
Bath, Combe Park, United Kingdom, BA1 3NG
Contact: Marianne Roots    +44 122 547 6420    M.Roots@bath.ac.uk   
Contact: Nicola Youlden    +44 122 547 6420    ny247@bath.ac.uk   
Principal Investigator: Roy Jones, Prof         
Manchester Mental Health & Social Care Trust - Dementia Research Office - Park House North Manchester General Hospital Recruiting
Manchester, Lancashire, United Kingdom, M8 5RB
Contact: Rowen Norton    +44 775 875 4813    rowen.norton@nihr.ac.uk   
Contact: Ambily Sathish    +44 161 720 2421    ambily.mani@nihr.ac.uk   
Principal Investigator: Leroi Iracema, Dr         
West London Mental Health Trust Recruiting
Isleworth, London, United Kingdom, TW7 6FY
Contact: Genevieve Morrison    +44 208 483 1834    Genevieve.Morrison@wlmht.nhs.uk   
Contact: Stephanie Deriziotis    +44 208 483 1827    Stephanie.Deriziotis@wlmht.nhs.uk   
Principal Investigator: Paresh Malhotra, MD         
St Pancras Clinical Research Recruiting
Kings Cross, London, United Kingdom, WC1X 8QD
Contact: Kaltuun Warsame    +44 203 865 1142    kaltuunwarsame@stpancrasclinical.com   
Contact: Katherine Nuttall    +44 203 865 1142    katherinenuttall@stpancrasclinical.com   
Principal Investigator: Richard Langford, Prof         
Sub-Investigator: Louise Keatings         
Institute of Clinical Sciences, Queen's University Belfast Recruiting
Belfast, Northern Ireland, United Kingdom, BT9 7AB
Contact: Aine Wallace    +44 2890978969 ext 90978970    a.wallace@qub.ac.uk   
Contact: Alison Clinton    +44 2890978948    Alison.Clinton@belfasttrust.hscni.net   
Principal Investigator: Anthony Passmore, Prof         
Sub-Investigator: Bernadette McGuinness, Dr         
Centre for Clinical Brain Sciences, Centre for Dementia Prevention, The University of Edinburgh Recruiting
Edinburgh, United Kingdom, EH8 9YL
Contact: Natalie Jenkins    +44 131 537 3804    Natalie.Jenkins@ed.ac.uk   
Contact: Jacqui Kerr    +44 131 650 6531    Jacqueline.x.kerr@nhslothian.scot.nhs.uk   
Principal Investigator: Craig Ritchie, Prof         
Sub-Investigator: Hinesh Topiwala, Dr         
Sponsors and Collaborators
Actinogen Medical
ICON Clinical Research
Investigators
Study Chair: Vincent Ruffles Actinogen Medical
Study Director: Alan Boyd, MD, FFPM Actinogen Medical

Additional Information:
Publications:
Responsible Party: Actinogen Medical
ClinicalTrials.gov Identifier: NCT02727699     History of Changes
Other Study ID Numbers: ACW0002
First Posted: April 5, 2016    Key Record Dates
Last Update Posted: May 31, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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

Keywords provided by Actinogen Medical:
Mild Dementia
Actinogen
Alzheimer's Disease
Xanamem
Cortisol
UE2343
XanADu

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders