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

• ClinicalTrials.gov Identifier: NCT04200911
• Recruitment Status: Completed
• First Posted: December 16, 2019
• Results First Posted: March 21, 2023
• Last Update Posted: December 22, 2023
• Sponsor: The University of Texas Health Science Center at San Antonio
• Collaborator: National Center for Advancing Translational Sciences (NCATS)
• Information provided by (Responsible Party): The University of Texas Health Science Center at San Antonio

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Cognitive Impairment, Mild; Alzheimer Disease
• Intervention: Drug: Rapamune
• Enrollment: 10

Participant Flow

Recruitment Details	Subjects that were enrolled and passed eligibility screening and went on to randomization.
Pre-assignment Details

Arm/Group Title	RAPA Intervention
Arm/Group Description	Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Period Title: Overall Study
Started	10
Completed	10
Not Completed	0

Baseline Characteristics

Arm/Group Title		RAPA Intervention
Arm/Group Description		Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Overall Number of Baseline Participants		10
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	10 participants
	<=18 years	0 0.0%
	Between 18 and 65 years	0 0.0%
	>=65 years	10 100.0%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	10 participants
		74 (4)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	10 participants
	Female	6 60.0%
	Male	4 40.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	10 participants
	Hispanic or Latino	0 0.0%
	Not Hispanic or Latino	10 100.0%
	Unknown or Not Reported	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	10 participants
	American Indian or Alaska Native	0 0.0%
	Asian	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	0 0.0%
	White	10 100.0%
	More than one race	0 0.0%
	Unknown or Not Reported	0 0.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	10 participants
		10
Diagnosis [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	10 participants
	Mild cognitive impairment	6 60.0%
	Early-stage dementia	4 40.0%
		[1] Measure Description: Clinical diagnosis of mild cognitive impairment or early-stage Alzheimer's disease by a qualified physician

Outcome Measures

1. Primary Outcome

Title	Blood Brain Barrier Penetration of RAPA
Description	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.
Time Frame	Change from Baseline to 8 weeks

Outcome Measure Data

Analysis Population Description

HPLC/MS/MS

Arm/Group Title	RAPA Intervention
Arm/Group Description:	Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Overall Number of Participants Analyzed	10
Mean (Standard Deviation); Unit of Measure: ng/ml
	0 (0)

2. Secondary Outcome

Title	Adverse Events
Description	Number of adverse events experienced across all 10 subjects after they were enrolled and randomized to treatment, regardless of relatedness to intervention.
Time Frame	Baseline to 8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RAPA Intervention
Arm/Group Description:	Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Overall Number of Participants Analyzed	10
Measure Type: Number; Unit of Measure: Events
	16

3. Secondary Outcome

Title	Change in CSF A Beta-42 Levels From Baseline to 8 Weeks
Description	Evaluation of relevant AD biomarkers.Change is calculated as value at 8 weeks minus the value at baseline.
Time Frame	Baseline to 8 weeks

Outcome Measure Data

Analysis Population Description

paired samples t-test comparing pre to post-treatment CSF abeta 42 levels

Arm/Group Title	RAPA Intervention
Arm/Group Description:	Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Overall Number of Participants Analyzed	10
Mean (Standard Deviation); Unit of Measure: ng/ml
	0.06 (0.03)

4. Secondary Outcome

Title	Electronic Gait Mapping
Description	Assessment of physical functioning under single and dual task conditions
Time Frame	Change from Baseline to 8 weeks

Outcome Measure Data

Analysis Population Description

Data were not collected for this measure so no data analysis occured

Arm/Group Title	RAPA Intervention
Arm/Group Description:	Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

5. Secondary Outcome

Title	Grip Strength
Description	Assessment of physical function using grip strength
Time Frame	Change from Baseline to 8 weeks

Outcome Measure Data

Analysis Population Description

paired t-test from pre to post-treatment

Arm/Group Title	RAPA Intervention
Arm/Group Description:	Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Overall Number of Participants Analyzed	10
Mean (Standard Deviation); Unit of Measure: kg
	0.3 (2.10)

6. Secondary Outcome

Title	Clinical Dementia Rating (CDR) Global Score
Description	A 5 point scale used to characterize six domains of cognitive and functional performance to give a possible score of 0-18. Each domain is rated on a score of 0 to 3 (0, 0.5, 1, 2 or 3) and the global score is derived based on the Washington University logarithm. Higher scores indicate worse cognitive and functional status.
Time Frame	Change from Baseline to 8 weeks

Outcome Measure Data

Analysis Population Description

paired t-tests comparing pre to post-treatment

Arm/Group Title	RAPA Intervention
Arm/Group Description:	Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Overall Number of Participants Analyzed	10
Mean (Standard Deviation); Unit of Measure: scores on a scale
	0.05 (0.158)

7. Secondary Outcome

Title	Benson Figure Copy
Description	A scale used to score a test of visuoconstructional abilities. Scores range from 0-16 with higher scores indicating better performance. Change is calculated as performance at 8 weeks minus baseline.
Time Frame	Change from Baseline to 8 weeks

Outcome Measure Data

Analysis Population Description

paired t-tests comparing pre to post-treatment

Arm/Group Title	RAPA Intervention
Arm/Group Description:	Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Overall Number of Participants Analyzed	10
Mean (Standard Deviation); Unit of Measure: scores on a scale
	0.7 (1.83)

8. Secondary Outcome

Title	Neuropsychiatric Inventory (NPI)
Description	A scale to assess dementia-related behavioral symptoms. The score represents the sum of 12 items, each scored 0-3. The total score can range from 0 to 36. Higher scores indicated greater neuropsychiatric severity. Change is calculated as the 8-week score minus baseline.
Time Frame	Change from Baseline to 8 weeks

Outcome Measure Data

Analysis Population Description

paired t-test comparing pre to post-treatment values

Arm/Group Title	RAPA Intervention
Arm/Group Description:	Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Overall Number of Participants Analyzed	10
Mean (Standard Deviation); Unit of Measure: scores on a scale
	0.7 (2.83)

9. Secondary Outcome

Title	Functional Activities Questionnaire (FAQ)
Description	An informant rates the subject's ability using a scoring system. The measure consists of 10 items with scoring ranging from 0-3 and the total score represents the sum of the items. The scores range from 0 to 30 with higher scores indicating more functional impairment. Change is calculated as the 8-week score minus baseline.
Time Frame	Change from Baseline to 8 weeks

Outcome Measure Data

Analysis Population Description

paired t-tests from pre- to post-treatment

Arm/Group Title	RAPA Intervention
Arm/Group Description:	Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
Overall Number of Participants Analyzed	10
Mean (Standard Deviation); Unit of Measure: scores on a scale
	-0.1 (4.4)

Adverse Events

Time Frame	8 weeks
Adverse Event Reporting Description	All adverse events that occurred after enrollment and randomization are reported, whether considered not related to or possible related to intervention.
Arm/Group Title	RAPA Intervention
Arm/Group Description	Sirolimus 1mg orally once a day for 8 weeks Rapamune: Sirolimus 1mg capsules
All-Cause Mortality
	RAPA Intervention
	Affected / at Risk (%)
Total	0/10 (0.00%)
Serious Adverse Events
	RAPA Intervention
	Affected / at Risk (%)	# Events
Total	1/10 (10.00%)
Nervous system disorders
Altered Mental Status * [1]	1/10 (10.00%)	1
* Indicates events were collected by non-systematic assessment; [1] Unrelated to study intervention, possible TIA
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	RAPA Intervention
	Affected / at Risk (%)	# Events
Total	10/10 (100.00%)
Blood and lymphatic system disorders
Hyperkalemia * [1]	1/10 (10.00%)	1
Leg edema * [2]	2/10 (20.00%)	2
Gastrointestinal disorders
Emesis * [3]	1/10 (10.00%)	1
Diarrhea * [4]	1/10 (10.00%)	1
General disorders
Fall * [5]	1/10 (10.00%)	1
Nervous system disorders
Headache * [6]	1/10 (10.00%)	1
Renal and urinary disorders
Urinary retention * [7]	1/10 (10.00%)	1
Urinary incontinence * [5]	1/10 (10.00%)	1
Urinary urgency * [5]	1/10 (10.00%)	1
Respiratory, thoracic and mediastinal disorders
Upper respiratory infection * [8]	2/10 (20.00%)	2
Cough * [9]	1/10 (10.00%)	1
Skin and subcutaneous tissue disorders
Intermittent Rash * [1]	1/10 (10.00%)	1
Skin infection * [10]	1/10 (10.00%)	1
* Indicates events were collected by non-systematic assessment; [1] Mild and unlikely to be related to intervention; [2] Mild for one subject, moderate for the other and unlikely to be related to intervention; [3] Mild, unlikely to have been related to study intervention; [4] Mild, one subject was possibly related, the other was not; [5] Mild and unlikely related; [6] Moderate and not related to intervention; [7] Mild and unlikely related to intervention; [8] Mild and unlikely to be related to intervention for one subject, possible for the other; [9] Mild and not likely to be related to intervention; [10] Not related to intervention (kitten scratches)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Mitzi Gonzales, PhD
• Organization: UT Health San Antonio
• Phone: 210-450-9047
• EMail: Gonzalesm20@uthscsa.edu

• Responsible Party: The University of Texas Health Science Center at San Antonio
• ClinicalTrials.gov Identifier: NCT04200911
• Other Study ID Numbers: HSC20190850H; UL1TR002645 ( U.S. NIH Grant/Contract )
• First Submitted: December 6, 2019
• First Posted: December 16, 2019
• Results First Submitted: January 27, 2023
• Results First Posted: March 21, 2023
• Last Update Posted: December 22, 2023