Trial Outcomes & Findings for Cognition, Age, and RaPamycin Effectiveness - DownregulatIon of thE mTor Pathway (NCT NCT04200911)

NCT ID: NCT04200911

Last Updated: 2025-01-08

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: EARLY_PHASE1
• Target enrollment: 10 participants
• Primary outcome timeframe: Change from Baseline to 8 weeks
• Results posted on: 2025-01-08

Participant Flow

Subjects that were enrolled and passed eligibility screening and went on to randomization.

Participant milestones

Measure	RAPA Intervention Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Overall Study STARTED	10
Overall Study COMPLETED	10
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	RAPA Intervention n=10 Participants Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	10 Participants n=5 Participants
Age, Continuous	74 years STANDARD_DEVIATION 4 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	10 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	10 participants n=5 Participants
Diagnosis Mild cognitive impairment	6 Participants n=5 Participants
Diagnosis Early-stage dementia	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: Change from Baseline to 8 weeks

Population: HPLC/MS/MS

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.

Outcome measures

Measure	RAPA Intervention n=10 Participants Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Blood Brain Barrier Penetration of RAPA	0 ng/ml Standard Deviation 0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	RAPA Intervention n=10 Participants Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Adverse Events	20 Events

SECONDARY outcome

Timeframe: Baseline to 8 weeks

Population: paired samples t-test comparing pre to post-treatment blood pressure.

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

Outcome measures

Measure	RAPA Intervention n=10 Participants Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Change in Vitals From Baseline to 8 Weeks systolic blood pressure	10.45 mmHg Standard Deviation 7.82
Change in Vitals From Baseline to 8 Weeks diastolic blood pressure	1.7 mmHg Standard Deviation 5.87

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	RAPA Intervention n=10 Participants Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Percentage of Study Drug Pills Taken	92 percentage of study drug pills taken Standard Deviation 5

SECONDARY outcome

Timeframe: Baseline to 8 weeks

Population: paired samples t-test comparing pre to post-treatment CSF ADRD biomarker levels

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

Outcome measures

Measure	RAPA Intervention n=10 Participants Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Change in CSF AD Biomarkers From Baseline to 8 Weeks CSF ptau-181	2.64 ng/ml Standard Deviation 2.72
Change in CSF AD Biomarkers From Baseline to 8 Weeks CSF abeta 40	615.57 ng/ml Standard Deviation 1210.06
Change in CSF AD Biomarkers From Baseline to 8 Weeks CSF Abeta42	21.52 ng/ml Standard Deviation 62.12
Change in CSF AD Biomarkers From Baseline to 8 Weeks CSF GFAP	6262.21 ng/ml Standard Deviation 4928.96
Change in CSF AD Biomarkers From Baseline to 8 Weeks CSF NFL	367.18 ng/ml Standard Deviation 310.71

SECONDARY outcome

Timeframe: Baseline to 8 weeks

Population: paired samples t-test comparing pre to post-treatment plasma ADRD biomarker levels

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

Outcome measures

Measure	RAPA Intervention n=10 Participants Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Change in Plasma AD Biomarkers From Baseline to 8 Weeks Plasma NFL	0.84 ng/ml Standard Deviation 4.64
Change in Plasma AD Biomarkers From Baseline to 8 Weeks plasma ptau-181	-0.22 ng/ml Standard Deviation 0.47
Change in Plasma AD Biomarkers From Baseline to 8 Weeks plasma abeta 40	-8.86 ng/ml Standard Deviation 12.28
Change in Plasma AD Biomarkers From Baseline to 8 Weeks Plasma Abeta42	-0.67 ng/ml Standard Deviation 0.69
Change in Plasma AD Biomarkers From Baseline to 8 Weeks Plasma GFAP	-27.70 ng/ml Standard Deviation 64.78

SECONDARY outcome

Timeframe: Baseline to 8 weeks

Population: paired samples t-test comparing pre to post-treatment CSF inflammatory values.

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

Outcome measures

Measure	RAPA Intervention n=10 Participants Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Change in CSF Inflammatory Markers From Baseline to 8 Weeks IL-10	0.02 pg/ml Standard Deviation 0.02
Change in CSF Inflammatory Markers From Baseline to 8 Weeks IL-6	-0.02 pg/ml Standard Deviation 0.25
Change in CSF Inflammatory Markers From Baseline to 8 Weeks IL-8	5.76 pg/ml Standard Deviation 9.10
Change in CSF Inflammatory Markers From Baseline to 8 Weeks TNF-α	0.03 pg/ml Standard Deviation 0.07
Change in CSF Inflammatory Markers From Baseline to 8 Weeks IL-12	0.35 pg/ml Standard Deviation 0.53
Change in CSF Inflammatory Markers From Baseline to 8 Weeks IL-15	0.29 pg/ml Standard Deviation 0.28
Change in CSF Inflammatory Markers From Baseline to 8 Weeks IL-16	0.63 pg/ml Standard Deviation 3.40
Change in CSF Inflammatory Markers From Baseline to 8 Weeks IL-17a	0.03 pg/ml Standard Deviation 0.09
Change in CSF Inflammatory Markers From Baseline to 8 Weeks IL-1a	-0.15 pg/ml Standard Deviation 0.33
Change in CSF Inflammatory Markers From Baseline to 8 Weeks IL-5	0.07 pg/ml Standard Deviation 0.07
Change in CSF Inflammatory Markers From Baseline to 8 Weeks IL-7	0.004 pg/ml Standard Deviation 0.10
Change in CSF Inflammatory Markers From Baseline to 8 Weeks VEGF-A	0.95 pg/ml Standard Deviation 2.37
Change in CSF Inflammatory Markers From Baseline to 8 Weeks VEGF-C	266.60 pg/ml Standard Deviation 575.93
Change in CSF Inflammatory Markers From Baseline to 8 Weeks VEGF-D	109.64 pg/ml Standard Deviation 117.23
Change in CSF Inflammatory Markers From Baseline to 8 Weeks Eotaxin	-5.05 pg/ml Standard Deviation 32.40
Change in CSF Inflammatory Markers From Baseline to 8 Weeks Eotaxin-3	-0.20 pg/ml Standard Deviation 2.20
Change in CSF Inflammatory Markers From Baseline to 8 Weeks IP-10	-12.93 pg/ml Standard Deviation 143.87
Change in CSF Inflammatory Markers From Baseline to 8 Weeks MCP-1	-22.56 pg/ml Standard Deviation 78.00
Change in CSF Inflammatory Markers From Baseline to 8 Weeks MIP1-α	0.83 pg/ml Standard Deviation 2.90
Change in CSF Inflammatory Markers From Baseline to 8 Weeks sFLT-1	41.18 pg/ml Standard Deviation 253.61
Change in CSF Inflammatory Markers From Baseline to 8 Weeks PIGF	2.84 pg/ml Standard Deviation 40.66
Change in CSF Inflammatory Markers From Baseline to 8 Weeks bFGF	-0.69 pg/ml Standard Deviation 20.85
Change in CSF Inflammatory Markers From Baseline to 8 Weeks sVCAM1	21202.57 pg/ml Standard Deviation 24439.62
Change in CSF Inflammatory Markers From Baseline to 8 Weeks sICAM1	6701.21 pg/ml Standard Deviation 13402.98
Change in CSF Inflammatory Markers From Baseline to 8 Weeks SAA	-73762.91 pg/ml Standard Deviation 375497.74
Change in CSF Inflammatory Markers From Baseline to 8 Weeks CRP	-98910.45 pg/ml Standard Deviation 27540.81
Change in CSF Inflammatory Markers From Baseline to 8 Weeks IFN-γ	0.14 pg/ml Standard Deviation 0.17

SECONDARY outcome

Timeframe: Baseline to 8 weeks

Population: paired samples t-test comparing pre to post-treatment plasma inflammatory biomarkers.

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

Outcome measures

Measure	RAPA Intervention n=10 Participants Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Change in Plasma Inflammatory Markers From Baseline to 8 Weeks IL-10	-0.18 pg/ml Standard Deviation 0.53
Change in Plasma Inflammatory Markers From Baseline to 8 Weeks IL-6	0.29 pg/ml Standard Deviation 0.54
Change in Plasma Inflammatory Markers From Baseline to 8 Weeks IL-8	0.16 pg/ml Standard Deviation 1.57
Change in Plasma Inflammatory Markers From Baseline to 8 Weeks TNF-α	0.06 pg/ml Standard Deviation 0.44
Change in Plasma Inflammatory Markers From Baseline to 8 Weeks IL-12	-16.56 pg/ml Standard Deviation 38.52
Change in Plasma Inflammatory Markers From Baseline to 8 Weeks IL-15	0.12 pg/ml Standard Deviation 0.31
Change in Plasma Inflammatory Markers From Baseline to 8 Weeks IL-16	16.18 pg/ml Standard Deviation 42.70
Change in Plasma Inflammatory Markers From Baseline to 8 Weeks IL-17a	0.36 pg/ml Standard Deviation 1.68
Change in Plasma Inflammatory Markers From Baseline to 8 Weeks IL-1a	-0.20 pg/ml Standard Deviation 0.36
Change in Plasma Inflammatory Markers From Baseline to 8 Weeks IL-5	0.34 pg/ml Standard Deviation 0.46
Change in Plasma Inflammatory Markers From Baseline to 8 Weeks IL-7	-0.14 pg/ml Standard Deviation 1.63
Change in Plasma Inflammatory Markers From Baseline to 8 Weeks VEGF-A	-0.05 pg/ml Standard Deviation 7.98
Change in Plasma Inflammatory Markers From Baseline to 8 Weeks VEGF-C	2000.38 pg/ml Standard Deviation 6648.40
Change in Plasma Inflammatory Markers From Baseline to 8 Weeks VEGF-D	3741.02 pg/ml Standard Deviation 3124.38
Change in Plasma Inflammatory Markers From Baseline to 8 Weeks Eotaxin	22.07 pg/ml Standard Deviation 36.04
Change in Plasma Inflammatory Markers From Baseline to 8 Weeks Eotaxin-3	-3.60 pg/ml Standard Deviation 6.19
Change in Plasma Inflammatory Markers From Baseline to 8 Weeks IP-10	18.26 pg/ml Standard Deviation 80.08
Change in Plasma Inflammatory Markers From Baseline to 8 Weeks MCP-1	-4.80 pg/ml Standard Deviation 10.74
Change in Plasma Inflammatory Markers From Baseline to 8 Weeks MIP1-α	-0.83 pg/ml Standard Deviation 3.64
Change in Plasma Inflammatory Markers From Baseline to 8 Weeks sFLT-1	258.88 pg/ml Standard Deviation 237.44
Change in Plasma Inflammatory Markers From Baseline to 8 Weeks PIGF	20.81 pg/ml Standard Deviation 11.81
Change in Plasma Inflammatory Markers From Baseline to 8 Weeks bFGF	-143.67 pg/ml Standard Deviation 174.71
Change in Plasma Inflammatory Markers From Baseline to 8 Weeks sVCAM1	97456.61 pg/ml Standard Deviation 1400309.82
Change in Plasma Inflammatory Markers From Baseline to 8 Weeks sICAM1	91844.33 pg/ml Standard Deviation 1329185.57
Change in Plasma Inflammatory Markers From Baseline to 8 Weeks SAA	190090000 pg/ml Standard Deviation 936172849.0
Change in Plasma Inflammatory Markers From Baseline to 8 Weeks CRP	36165816.2 pg/ml Standard Deviation 111516450.7
Change in Plasma Inflammatory Markers From Baseline to 8 Weeks IFN-γ	4.37 pg/ml Standard Deviation 1.91

SECONDARY outcome

Timeframe: Baseline to 8 weeks

Population: paired samples t-test comparing pre to post-treatment safety laboratory values.

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

Outcome measures

Measure	RAPA Intervention n=10 Participants Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Safety Labs - Change in White Blood Cell and Platelet Counts From Baseline to 8 Weeks White Blood Cell Count	0.42 x10^3 cells/μL Standard Deviation 1.92
Safety Labs - Change in White Blood Cell and Platelet Counts From Baseline to 8 Weeks Immature Granulocytes	-0.21 x10^3 cells/μL Standard Deviation 1.19
Safety Labs - Change in White Blood Cell and Platelet Counts From Baseline to 8 Weeks Eosinophils	0.10 x10^3 cells/μL Standard Deviation 2.5
Safety Labs - Change in White Blood Cell and Platelet Counts From Baseline to 8 Weeks Basophils	-0.19 x10^3 cells/μL Standard Deviation 0.40
Safety Labs - Change in White Blood Cell and Platelet Counts From Baseline to 8 Weeks Platelets	20.60 x10^3 cells/μL Standard Deviation 35.19

SECONDARY outcome

Timeframe: Baseline to 8 weeks

Population: paired sample's t-test comparing pre to post-treatment safety laboratory values

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.

Outcome measures

Measure	RAPA Intervention n=10 Participants Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Safety Labs - Change in Red Blood Cell Count	-0.01 x10^6 cells/μL Standard Deviation 0.27

SECONDARY outcome

Timeframe: 8 weeks

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

Outcome measures

Measure	RAPA Intervention n=10 Participants Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Safety Labs - Change in Mean Corpuscular Volume	-2.70 fL Standard Deviation 2.16

SECONDARY outcome

Timeframe: 8-weeks

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

Outcome measures

Measure	RAPA Intervention n=10 Participants Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Safety Labs - Change in Mean Corpuscular Hemoglobin	-0.81 pg Standard Deviation 0.69

SECONDARY outcome

Timeframe: 8 weeks

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

Outcome measures

Measure	RAPA Intervention n=10 Participants Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Safety Labs - Change in Metabolic Parameters (g/dl) Hemoglobin	-0.27 g/dl Standard Deviation 0.57
Safety Labs - Change in Metabolic Parameters (g/dl) Protein	-1.77 g/dl Standard Deviation 5.85
Safety Labs - Change in Metabolic Parameters (g/dl) Albumin	-0.13 g/dl Standard Deviation 0.19
Safety Labs - Change in Metabolic Parameters (g/dl) Mean Corpuscular Hemoglobin Concentration	0.08 g/dl Standard Deviation 0.85

SECONDARY outcome

Timeframe: 8 weeks

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

Outcome measures

Measure	RAPA Intervention n=10 Participants Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Safety Labs - Change in Hematocrit	-0.86 percentage of red blood cells Standard Deviation 2.09

SECONDARY outcome

Timeframe: 8 weeks

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

Outcome measures

Measure	RAPA Intervention n=10 Participants Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Safety Labs - Change in Monocytes	-0.19 percentage of white blood cell count Standard Deviation 4.08

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	RAPA Intervention n=10 Participants Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Safety Labs - Change in Red Cell Distribution Width	-0.65 Percentage Standard Deviation 0.24

SECONDARY outcome

Timeframe: 8 weeks

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

Outcome measures

Measure	RAPA Intervention n=10 Participants Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Safety Labs - Change in Hemoglobin A1c	0.17 % of hemoglobin covered w/ glucose Standard Deviation 0.22

SECONDARY outcome

Timeframe: 8 weeks

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

Outcome measures

Measure	RAPA Intervention n=10 Participants Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Safety Labs - Change in Metabolic and Lipid Parameters (mg/dl) glucose	2.70 mg/dl Standard Deviation 6.67
Safety Labs - Change in Metabolic and Lipid Parameters (mg/dl) blood urea nitrogen	-1.80 mg/dl Standard Deviation 4.13
Safety Labs - Change in Metabolic and Lipid Parameters (mg/dl) Creatinine	-0.001 mg/dl Standard Deviation 0.09
Safety Labs - Change in Metabolic and Lipid Parameters (mg/dl) Bilirubin	-0.09 mg/dl Standard Deviation 0.34
Safety Labs - Change in Metabolic and Lipid Parameters (mg/dl) Cholesterol	-0.30 mg/dl Standard Deviation 26.08
Safety Labs - Change in Metabolic and Lipid Parameters (mg/dl) High-Density Lipoprotein Cholesterol	2.90 mg/dl Standard Deviation 7.22
Safety Labs - Change in Metabolic and Lipid Parameters (mg/dl) Low-Density Lipoprotein Cholesterol	-2.70 mg/dl Standard Deviation 20.38
Safety Labs - Change in Metabolic and Lipid Parameters (mg/dl) Very Low-Density Lipoprotein Cholesterol	-0.50 mg/dl Standard Deviation 4.25

SECONDARY outcome

Timeframe: 8 weeks

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

Outcome measures

Measure	RAPA Intervention n=10 Participants Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Safety Labs - Change in Sodium and Potassium (mmol/L) Sodium	-5.40 mmol/L Standard Deviation 18.90
Safety Labs - Change in Sodium and Potassium (mmol/L) Potassium	-0.19 mmol/L Standard Deviation 0.44

SECONDARY outcome

Timeframe: 8 weeks

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

Outcome measures

Measure	RAPA Intervention n=10 Participants Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Safety Labs - Change in Liver Panel (iU/L) Aspartate Aminotransferase	1.00 IU/L Standard Deviation 4.06
Safety Labs - Change in Liver Panel (iU/L) Alanine Transaminase	0.001 IU/L Standard Deviation 6.20
Safety Labs - Change in Liver Panel (iU/L) Alkaline Phosphatase	4.10 IU/L Standard Deviation 10.90

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	RAPA Intervention n=10 Participants Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Cognition/Functional Status - Change in Montreal Cognitive Assessment (MoCA)	-1.30 score on a scale Standard Deviation 2.45

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	RAPA Intervention n=10 Participants Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Cognition/Functional Status - Change on the Clinical Rating Scale Global Score	0.15 score on a scale Standard Deviation 0.16

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	RAPA Intervention n=10 Participants Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Cognition/Functional Status - Change on the Clinical Rating Scale Sum of Boxes Score	0.55 score on a scale Standard Deviation 0.86

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	RAPA Intervention n=10 Participants Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Cognition/Functional Status - Change on the Hopkins Verbal Learning Test - Revised Immediate Recall	0.40 score on a scale Standard Deviation 3.37

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	RAPA Intervention n=10 Participants Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Cognition/Functional Status - Change on the Hopkins Verbal Learning Test - Revised Delayed Recall	-1.00 score on a scale Standard Deviation 2.54

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	RAPA Intervention n=10 Participants Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Cognition/Functional Status - Change on the Craft Story Immediate Recall Verbatim	0.20 score on a scale Standard Deviation 4.29

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	RAPA Intervention n=10 Participants Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Cognition/Functional Status - Change on the Craft Story Delayed Recall Verbatim	-1.40 score on a scale Standard Deviation 2.95

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	RAPA Intervention n=10 Participants Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Cognition/Functional Status - Change on the Benson Figure Copy	0.70 score on a scale Standard Deviation 1.83

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	RAPA Intervention n=10 Participants Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Cognition/Functional Status - Change on the Benson Figure Delayed Recall	-0.80 score on a scale Standard Deviation 2.04

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	RAPA Intervention n=10 Participants Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Cognition/Functional Status - Change on the Number Span Forward	0.20 score on a scale Standard Deviation 1.62

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	RAPA Intervention n=10 Participants Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Cognition/Functional Status - Change on the Number Span Backward	-0.60 score on a scale Standard Deviation 0.84

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	RAPA Intervention n=10 Participants Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Cognition/Functional Status - Change on the Trail Making Test Part A, Time to Completion	3.09 seconds to complete Standard Deviation 3.15

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	RAPA Intervention n=10 Participants Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Cognition/Functional Status - Change Trail Making Test Part B, Time to Completion	26.69 seconds to complete Standard Deviation 14.97

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	RAPA Intervention n=10 Participants Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Cognition/Functional Status - Change on Phonemic Fluency	1.80 score on a scale Standard Deviation 3.71

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	RAPA Intervention n=10 Participants Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Cognition/Functional Status - Change on Semantic Fluency	1.10 score on a scale Standard Deviation 4.18

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	RAPA Intervention n=10 Participants Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Cognition/Functional Status - Change on the Multilingual Naming Test	1.50 score on a scale Standard Deviation 4.67

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	RAPA Intervention n=10 Participants Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Cognition/Functional Status - Change on the Hayling, Total Errors	0.001 score on a scale Standard Deviation 0.78

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	RAPA Intervention n=10 Participants Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Cognition/Functional Status - Change on Grip Strength, Dominant Hand	0.30 kilograms Standard Deviation 2.10

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	RAPA Intervention n=10 Participants Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Cognition/Functional Status - Change on Grip Strength, Non-dominant Hand	-0.25 kilograms Standard Deviation 3.30

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	RAPA Intervention n=10 Participants Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Cognition/Functional Status - Change on the Geriatric Depression Scale 15-item	0.10 score on a scale Standard Deviation 1.73

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	RAPA Intervention n=10 Participants Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Cognition/Functional Status - Change on the Functional Activities Questionnaire	-0.10 score on a scale Standard Deviation 4.36

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	RAPA Intervention n=10 Participants Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Cognition/Functional Status - Change on the Neuropsychiatric Inventory Questionnaire	0.70 score on a scale Standard Deviation 2.83

Adverse Events

RAPA Intervention

Serious events: 1 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Measure	RAPA Intervention n=10 participants at risk Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Nervous system disorders Altered Mental Status	10.0% 1/10 • Number of events 1 • 8 weeks All adverse events that occurred after enrollment and randomization are reported, whether considered not related to or possible related to intervention.

Other adverse events

Measure	RAPA Intervention n=10 participants at risk Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Skin and subcutaneous tissue disorders Intermittent Rash	10.0% 1/10 • Number of events 1 • 8 weeks All adverse events that occurred after enrollment and randomization are reported, whether considered not related to or possible related to intervention.
Nervous system disorders Headache	10.0% 1/10 • Number of events 1 • 8 weeks All adverse events that occurred after enrollment and randomization are reported, whether considered not related to or possible related to intervention.
Renal and urinary disorders Urinary retention	10.0% 1/10 • Number of events 1 • 8 weeks All adverse events that occurred after enrollment and randomization are reported, whether considered not related to or possible related to intervention.
Blood and lymphatic system disorders Hyperkalemia	10.0% 1/10 • Number of events 1 • 8 weeks All adverse events that occurred after enrollment and randomization are reported, whether considered not related to or possible related to intervention.
Respiratory, thoracic and mediastinal disorders Upper respiratory infection	10.0% 1/10 • Number of events 1 • 8 weeks All adverse events that occurred after enrollment and randomization are reported, whether considered not related to or possible related to intervention.
Skin and subcutaneous tissue disorders Skin infection	10.0% 1/10 • Number of events 2 • 8 weeks All adverse events that occurred after enrollment and randomization are reported, whether considered not related to or possible related to intervention.
Blood and lymphatic system disorders Leg edema	20.0% 2/10 • Number of events 2 • 8 weeks All adverse events that occurred after enrollment and randomization are reported, whether considered not related to or possible related to intervention.
Gastrointestinal disorders Emesis	10.0% 1/10 • Number of events 2 • 8 weeks All adverse events that occurred after enrollment and randomization are reported, whether considered not related to or possible related to intervention.
Respiratory, thoracic and mediastinal disorders Cough	10.0% 1/10 • Number of events 2 • 8 weeks All adverse events that occurred after enrollment and randomization are reported, whether considered not related to or possible related to intervention.
Gastrointestinal disorders Diarrhea	10.0% 1/10 • Number of events 2 • 8 weeks All adverse events that occurred after enrollment and randomization are reported, whether considered not related to or possible related to intervention.
Renal and urinary disorders Urinary incontinence	10.0% 1/10 • Number of events 1 • 8 weeks All adverse events that occurred after enrollment and randomization are reported, whether considered not related to or possible related to intervention.
Renal and urinary disorders Urinary urgency	10.0% 1/10 • Number of events 1 • 8 weeks All adverse events that occurred after enrollment and randomization are reported, whether considered not related to or possible related to intervention.
General disorders Fall	20.0% 2/10 • Number of events 2 • 8 weeks All adverse events that occurred after enrollment and randomization are reported, whether considered not related to or possible related to intervention.

Additional Information

Mitzi Gonzales, PhD

UT Health San Antonio

Phone: 210-450-9047

Email: Gonzalesm20@uthscsa.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place