Early Phase 1 N=10 Treatment

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

Cognitive Impairment, Mild · Alzheimer Disease

Bottom Line

View on ClinicalTrials.gov: NCT04200911 ↗

Enrolled (actual)

Serious AEs

10.0%

Results posted

Mar 2023

Primary outcome: Primary: Blood Brain Barrier Penetration of RAPA — 0 ng/ml

Study Design & Population

Study type: Interventional
Phase: Early Phase 1
Interventions: Rapamune (Drug)
Age: Adult, Older Adult · 55+ yrs
Sex: All
Sponsor: The University of Texas Health Science Center at San Antonio
Primary completion: Jan 2022

Outcome Measures

Outcome	Result	p-value
PRIMARY Blood Brain Barrier Penetration of RAPA	—	—
SECONDARY Adverse Events	20	—
SECONDARY Change in Vitals From Baseline to 8 Weeks	10.45; 1.7	—
SECONDARY Percentage of Study Drug Pills Taken	92	—
SECONDARY Change in CSF AD Biomarkers From Baseline to 8 Weeks	2.64; 615.57; 21.52; 6262.21; 367.18	—
SECONDARY Change in Plasma AD Biomarkers From Baseline to 8 Weeks	-0.22; -8.86; -0.67; -27.70; 0.84	—
SECONDARY Change in CSF Inflammatory Markers From Baseline to 8 Weeks	0.02; -0.02; 5.76; 0.03; 0.35; 0.29	—
SECONDARY Change in Plasma Inflammatory Markers From Baseline to 8 Weeks	-0.18; 0.29; 0.16; 0.06; -16.56; 0.12	—
SECONDARY Safety Labs - Change in White Blood Cell and Platelet Counts From Baseline to 8 Weeks	0.42; -0.21; 0.10; -0.19; 20.60	—
SECONDARY Safety Labs - Change in Red Blood Cell Count	-0.01	—
SECONDARY Safety Labs - Change in Mean Corpuscular Volume	-2.70	—
SECONDARY Safety Labs - Change in Mean Corpuscular Hemoglobin	-0.81	—
SECONDARY Safety Labs - Change in Metabolic Parameters (g/dl)	-0.27; -1.77; -0.13; 0.08	—
SECONDARY Safety Labs - Change in Hematocrit	-0.86	—
SECONDARY Safety Labs - Change in Monocytes	-0.19	—
SECONDARY Safety Labs - Change in Red Cell Distribution Width	-0.65	—
SECONDARY Safety Labs - Change in Hemoglobin A1c	0.17	—
SECONDARY Safety Labs - Change in Metabolic and Lipid Parameters (mg/dl)	2.70; -1.80; -0.001; -0.09; -0.30; 2.90	—
SECONDARY Safety Labs - Change in Sodium and Potassium (mmol/L)	-5.40; -0.19	—
SECONDARY Safety Labs - Change in Liver Panel (iU/L)	1.00; 0.001; 4.10	—
SECONDARY Cognition/Functional Status - Change in Montreal Cognitive Assessment (MoCA)	-1.30	—
SECONDARY Cognition/Functional Status - Change on the Clinical Rating Scale Global Score	0.15	—
SECONDARY Cognition/Functional Status - Change on the Clinical Rating Scale Sum of Boxes Score	0.55	—
SECONDARY Cognition/Functional Status - Change on the Hopkins Verbal Learning Test - Revised Immediate Recall	0.40	—
SECONDARY Cognition/Functional Status - Change on the Hopkins Verbal Learning Test - Revised Delayed Recall	-1.00	—
SECONDARY Cognition/Functional Status - Change on the Craft Story Immediate Recall Verbatim	0.20	—
SECONDARY Cognition/Functional Status - Change on the Craft Story Delayed Recall Verbatim	-1.40	—
SECONDARY Cognition/Functional Status - Change on the Benson Figure Copy	0.70	—
SECONDARY Cognition/Functional Status - Change on the Benson Figure Delayed Recall	-0.80	—
SECONDARY Cognition/Functional Status - Change on the Number Span Forward	0.20	—
SECONDARY Cognition/Functional Status - Change on the Number Span Backward	-0.60	—
SECONDARY Cognition/Functional Status - Change on the Trail Making Test Part A, Time to Completion	3.09	—
SECONDARY Cognition/Functional Status - Change Trail Making Test Part B, Time to Completion	26.69	—
SECONDARY Cognition/Functional Status - Change on Phonemic Fluency	1.80	—
SECONDARY Cognition/Functional Status - Change on Semantic Fluency	1.10	—
SECONDARY Cognition/Functional Status - Change on the Multilingual Naming Test	1.50	—
SECONDARY Cognition/Functional Status - Change on the Hayling, Total Errors	0.001	—
SECONDARY Cognition/Functional Status - Change on Grip Strength, Dominant Hand	0.30	—
SECONDARY Cognition/Functional Status - Change on Grip Strength, Non-dominant Hand	-0.25	—
SECONDARY Cognition/Functional Status - Change on the Geriatric Depression Scale 15-item	0.10	—
SECONDARY Cognition/Functional Status - Change on the Functional Activities Questionnaire	-0.10	—
SECONDARY Cognition/Functional Status - Change on the Neuropsychiatric Inventory Questionnaire	0.70	—

Summary

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

Eligibility Criteria

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 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 ( 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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT04200911). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.