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Completed

NCT Number: NCT04200911

Cognition, Age, and RaPamycin Effectiveness - DownregulatIon of thE mTor Pathway

Evaluation of central nervous system penetration of orally administered Rapamune (RAPA) in older adults with Mild Cognitive Impairment (MCI) or early Alzheimer's disease (AD) and investigate associated safety, tolerability, target engagement, cognition, and functional status as initial proof-of-concept study

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Key information

Conditions

Cognitive Impairment, Mild Alzheimer Disease Brain Diseases Central Nervous System Diseases Cognition Disorders Cognitive Dysfunction Dementia Mental Disorders Nervous System Diseases Neurocognitive Disorders Neurodegenerative Diseases Tauopathies

Age range

55 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Early Phase 1

Primary location

UTHSA McDermott Clinical Sciences Building

San Antonio, Texas, 78229, United States

About this study

This study is an open-label pilot study of orally administered RAPA to measure its target engagement in Cerebrospinal Fluid (CSF) and blood, and to establish the feasibility and safety of RAPA treatment in older adults with MCI and early stage AD as initial proof-of-concept for a larger Phase 2 clinical trial.

Who can participate

Healthy volunteers accepted: Yes

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

Inclusion criteria

  • Diagnosis of Mild Cognitive Impairment (MCI) or Alzheimer's disease, Global Clinical Dementia Rating Scale (CDR)=0.5-1
  • Normal blood cell counts without clinically significant excursions; ; normal liver and renal function; and glucose control (HbA1c < 6.5%). Lipid panel and PT/PTT/INR within normal limits
  • A Legally Authorized Representative (LAR) if necessary for consent
  • An LAR or study partner to accompany participant to all visits
  • Availability for all study visits
  • Stable dose of AD medications) Donepezil, rivastigmine, memantine, galantamine) for at least 3 months prior to the baseline visit

Exclusion criteria

  • Diabetes (HbA1c≥6.5% or anti-diabetic medications)
  • History of skin ulcers or poor wound healing
  • Current tobacco or illicit drug use or alcohol abuse
  • Use of anti-platelet or anti-coagulant medications other than aspirin
  • Current medications that affect cytochrome P450 3A4; current or recent medications for hypertriglyceridemia (eg, Gemfibrozil)
  • Hypersensitivity or history of allergy to Rapamycin
  • Immunosuppressant therapy within the last year; current treatment with hydroxychloroquine and chloroquine (requires "washout period" of 14 days)
  • Chemotherapy or radiation treatment within the last year
  • Current or chronic history of liver disease or known hepatic or biliary abnormalities
  • History of primary hypertriglyceridemia. Abnormal triglycerides >200 or LDL cholesterol >193, or other abnormal labs deemed clinically significant upon investigator review
  • Current or chronic history of pulmonary disease or abnormal pulse oximetry (<90%)
  • Chronic heart failure
  • Pregnancy
  • Recent history (past 6 months) of myocardial infarction, active coronary artery disease, intestinal disorders, stroke, or transient ischemic attack
  • significant neurological conditions other than AD
  • Poorly controlled blood pressure (systolic BP>160, diastolic BP>90mmHg)
  • Active inflammatory, COVID-19, autoimmune, infectious, hepatic, gastrointestinal, malignant, and/or psychiatric disease
  • History of, or Magnetic Resonance Imaging (MRI) positive for any space occupying lesion, including mass effect and/or abnormal intracranial pressure, which would indicate contraindication to lumbar puncture
  • Organ transplant recipients

Treatment and study plan

Rapamune

Drug

Sirolimus 1mg capsules

Other names: Sirolimus

Primary outcomes

  1. Blood Brain Barrier Penetration of RAPA

    Time frame: Change from Baseline to 8 weeks

    Lumbar punctures will be performed at baseline and after the final RAPA dose, to assess CSF levels of the drug. Change is calculated as value at 8 weeks minus the value at baseline.

Secondary outcomes

  1. Adverse Events

    Time frame: Baseline to 8 weeks

    Number of adverse events experienced across all 10 subjects after they were enrolled and randomized to treatment, regardless of relatedness to intervention.

  2. Change in Vitals From Baseline to 8 Weeks

    Time frame: Baseline to 8 weeks

    Evaluation of vitals. Change is calculated as value at 8 weeks minus the value at baseline.

  3. Percentage of Study Drug Pills Taken

    Time frame: Baseline to 8 weeks

    Average percentage of study drug pills taken across all 10 subjects after they were enrolled and randomized to treatment. The percentage of study drug pills taken was evaluated by having participants return any leftover study drug pills at each visit during the active treatment period.

  4. Change in CSF AD Biomarkers From Baseline to 8 Weeks

    Time frame: Baseline to 8 weeks

    Evaluation of CSF AD biomarkers. Change is calculated as value at 8 weeks minus the value at baseline.

  5. Change in Plasma AD Biomarkers From Baseline to 8 Weeks

    Time frame: Baseline to 8 weeks

    Evaluation of plasma AD biomarkers. Change is calculated as value at 8 weeks minus the value at baseline.

  6. Change in CSF Inflammatory Markers From Baseline to 8 Weeks

    Time frame: Baseline to 8 weeks

    Evaluation of CSF inflammatory markers. Change is calculated as value at 8 weeks minus the value at baseline.

  7. Change in Plasma Inflammatory Markers From Baseline to 8 Weeks

    Time frame: Baseline to 8 weeks

    Evaluation of plasma inflammatory markers. Change is calculated as value at 8 weeks minus the value at baseline.

  8. Safety Labs - Change in White Blood Cell and Platelet Counts From Baseline to 8 Weeks

    Time frame: Baseline to 8 weeks

    Evaluation of safety labs - white blood cell and platelet counts. Change is calculated as value at 8 weeks minus the value at baseline.

  9. Safety Labs - Change in Red Blood Cell Count

    Time frame: Baseline to 8 weeks

    Evaluation of safety labs - red blood cell counts. Change in red blood cell count calculated as value at 8 weeks minus the value at baseline.

  10. Safety Labs - Change in Mean Corpuscular Volume

    Time frame: 8 weeks

    Evaluation of safety labs - Change in Mean Corpuscular volume. Change is calculated as value at 8 weeks minus the value at baseline

  11. Safety Labs - Change in Mean Corpuscular Hemoglobin

    Time frame: 8-weeks

    safety labs - Mean Corpuscular Hemoglobin. Change is calculated as value at 8 weeks minus the value at baseline.

  12. Safety Labs - Change in Metabolic Parameters (g/dl)

    Time frame: 8 weeks

    Evaluation of safety labs - metabolic parameters. Change is calculated as value at 8 weeks minus the value at baseline.

  13. Safety Labs - Change in Hematocrit

    Time frame: 8 weeks

    Evaluation of of safety labs - hematocrit. Change is calculated as value at 8 weeks minus the value at baseline.

  14. Safety Labs - Change in Monocytes

    Time frame: 8 weeks

    Evaluation of of safety labs - monocytes. Change is calculated as value at 8 weeks minus the value at baseline.

  15. Safety Labs - Change in Red Cell Distribution Width

    Time frame: 8 weeks

    Evaluation of of safety labs - Red cell distribution width. Change is calculated as value at 8 weeks minus the value at baseline. The value reported is % of red blood cell size and volume variability.

  16. Safety Labs - Change in Hemoglobin A1c

    Time frame: 8 weeks

    Evaluation of of safety labs - hemoglobin A1c. Change is calculated as value at 8 weeks minus the value at baseline.

  17. Safety Labs - Change in Metabolic and Lipid Parameters (mg/dl)

    Time frame: 8 weeks

    Evaluation of safety labs - metabolic and lipid parameters. Change is calculated as value at 8 weeks minus the value at baseline.

  18. Safety Labs - Change in Sodium and Potassium (mmol/L)

    Time frame: 8 weeks

    Evaluation of safety labs - sodium and potassium. Change is calculated as value at 8 weeks minus the value at baseline.

  19. Safety Labs - Change in Liver Panel (iU/L)

    Time frame: 8 weeks

    Evaluation of safety labs - liver panel. Change is calculated as value at 8 weeks minus the value at baseline.

  20. Cognition/Functional Status - Change in Montreal Cognitive Assessment (MoCA)

    Time frame: 8 weeks

    The Montreal Cognitive Assessment (MoCA) assesses global cognition with scores ranging from 0 to 30 points. Higher scores indicate better performance.Change is calculated as value at 8 weeks minus the value at baseline.

  21. Cognition/Functional Status - Change on the Clinical Rating Scale Global Score

    Time frame: 8 weeks

    The Clinical Rating Scale Global Score assesses cognition and daily functioning with scores ranging from 0 to 3 points. Higher scores indicate worse cognition and/or functional status.Change is calculated as value at 8 weeks minus the value at baseline.

  22. Cognition/Functional Status - Change on the Clinical Rating Scale Sum of Boxes Score

    Time frame: 8 weeks

    The Clinical Rating Scale Sum of Boxes assesses cognition and daily functioning with scores ranging from 0 to 18 points. Higher scores indicate worse cognition and/or functional status.Change is calculated as value at 8 weeks minus the value at baseline.

  23. Cognition/Functional Status - Change on the Hopkins Verbal Learning Test - Revised Immediate Recall

    Time frame: 8 weeks

    The Hopkins Verbal Learning Test - Revised Immediate Recall assesses verbal list learning with scores ranging from 0 to 36 points. Higher scores indicate better performance. Change is calculated as value at 8 weeks minus the value at baseline.

  24. Cognition/Functional Status - Change on the Hopkins Verbal Learning Test - Revised Delayed Recall

    Time frame: 8 weeks

    The Hopkins Verbal Learning Test - Revised Delayed Recall assesses verbal list learning with scores ranging from 0 to 12 points. Higher scores indicate better performance. Change is calculated as value at 8 weeks minus the value at baseline.

  25. Cognition/Functional Status - Change on the Craft Story Immediate Recall Verbatim

    Time frame: 8 weeks

    The Craft Story Immediate Recall Verbatim assesses verbal narrative learning with scores ranging from 0 to 44 points. Higher scores indicate better performance. Change is calculated as value at 8 weeks minus the value at baseline.

  26. Cognition/Functional Status - Change on the Craft Story Delayed Recall Verbatim

    Time frame: 8 weeks

    The Craft Story Delayed Recall Verbatim assesses verbal memory recall with scores ranging from 0 to 44 points. Higher scores indicate better performance. Change is calculated as value at 8 weeks minus the value at baseline.

  27. Cognition/Functional Status - Change on the Benson Figure Copy

    Time frame: 8 weeks

    The Benson Figure Copy assesses visuoconstructional skills with scores ranging from 0 to 17points. Higher scores indicate better performance. Change is calculated as value at 8 weeks minus the value at baseline.

  28. Cognition/Functional Status - Change on the Benson Figure Delayed Recall

    Time frame: 8 weeks

    The Benson Figure Delayed Recall assesses visual memory with scores ranging from 0 to 17 points. Higher scores indicate better performance.Change is calculated as value at 8 weeks minus the value at baseline.

  29. Cognition/Functional Status - Change on the Number Span Forward

    Time frame: 8 weeks

    The Number Span Forward test assesses basic attention with scores ranging from 0 to 16 points. Higher scores indicate better performance. Change is calculated as value at 8 weeks minus the value at baseline.

  30. Cognition/Functional Status - Change on the Number Span Backward

    Time frame: 8 weeks

    The Number Span Backward test assesses working memory with scores ranging from 0 to 14 points. Higher scores indicate better performance. Change is calculated as value at 8 weeks minus the value at baseline.

  31. Cognition/Functional Status - Change on the Trail Making Test Part A, Time to Completion

    Time frame: 8 weeks

    The Trail Making Test Part A, time to completion assesses psychomotor speed and visual scanning with scores ranging from 1 to 150 seconds. Higher scores indicate worse performance. Change is calculated as value at 8 weeks minus the value at baseline.

  32. Cognition/Functional Status - Change Trail Making Test Part B, Time to Completion

    Time frame: 8 weeks

    The Trail Making Test Part B, time to completion assesses attentional shifting with scores ranging from 1 to 300 seconds. Higher scores indicate worse performance. Change is calculated as value at 8 weeks minus the value at baseline.

  33. Cognition/Functional Status - Change on Phonemic Fluency

    Time frame: 8 weeks

    The Phonemic fluency test assesses speeded word generation to a phonemic cue. Scores begin at 0 with no upper limit. Higher scores indicate better performance. Change is calculated as value at 8 weeks minus the value at baseline.

  34. Cognition/Functional Status - Change on Semantic Fluency

    Time frame: 8 weeks

    The Semantic fluency test assesses speeded word generation to a semantic cue. Scores begin at 0 with no upper limit. Higher scores indicate better performance. Change is calculated as value at 8 weeks minus the value at baseline.

  35. Cognition/Functional Status - Change on the Multilingual Naming Test

    Time frame: 8 weeks

    The Multilingual Naming Test assesses confrontation naming. Scores range from 0 to 32 and higher scores indicate better performance. Change is calculated as value at 8 weeks minus the value at baseline.

  36. Cognition/Functional Status - Change on the Hayling, Total Errors

    Time frame: 8 weeks

    The Hayling assesses response inhibition errors. Scores range from 0 to 30 and higher scores indicate worse performance. Change is calculated as value at 8 weeks minus the value at baseline.

  37. Cognition/Functional Status - Change on Grip Strength, Dominant Hand

    Time frame: 8 weeks

    The grip strength, dominant hand assesses grip strength in kilograms. Values begin at 0 with no upper limit. Higher scores indicate better performance Change is calculated as value at 8 weeks minus the value at baseline.

  38. Cognition/Functional Status - Change on Grip Strength, Non-dominant Hand

    Time frame: 8 weeks

    The grip strength, non-dominant hand assesses grip strength in kilograms. Values begin at 0 with no upper limit. Higher scores indicate better performance. Change is calculated as value at 8 weeks minus the value at baseline.

  39. Cognition/Functional Status - Change on the Geriatric Depression Scale 15-item

    Time frame: 8 weeks

    The Geriatric Depression Scale 15-item assesses depressive symptomatology. Scores range from 0 to 15 and higher scores indicate worse outcomes. Change is calculated as value at 8 weeks minus the value at baseline.

  40. Cognition/Functional Status - Change on the Functional Activities Questionnaire

    Time frame: 8 weeks

    The Functional Activities Questionnaire assesses functional status for independent activities of daily living. Scores range from 0 to 30 and higher scores indicate worse outcomes. Change is calculated as value at 8 weeks minus the value at baseline.

  41. Cognition/Functional Status - Change on the Neuropsychiatric Inventory Questionnaire

    Time frame: 8 weeks

    The Neuropsychiatric Inventory Questionnaire assesses neuropsychiatric symptoms. Scores range from 0 to 12 and higher scores indicate worse outcomes. Change is calculated as value at 8 weeks minus the value at baseline.

Sponsors and collaborators

Lead sponsor

The University of Texas Health Science Center at San Antonio

Other

Collaborators

  • National Center for Advancing Translational Sciences (NCATS)

Registry information

Official study title

Cognition, Age, and RaPamycin Effectiveness - DownregulatIon of thE mTor Pathway (CARPE DIEM)

Acronym: CARPE_DIEM

Important dates

Study start
2020
Primary completion
2022
Study completion
2022
First posted
Dec 16, 2019
Registry last updated
Jan 8, 2025

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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