Evaluating Rapamycin Treatment in Alzheimer's Disease Using Positron Emission Tomography

NCT ID: NCT06022068

Last Updated: 2025-07-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-09-01
• Study Completion Date: 2025-01-17

Brief Summary

This single-center, uncontrolled pilot study aims to evaluate the efficacy, safety, and tolerability of six months of intermittently dosed oral rapamycin (sirolimus) in subjects with early-stage Alzheimer's disease.

Fifteen participants will be recruited. Following a set of baseline measurements, all participants will receive a weekly oral dose of 7 mg rapamycin for six months. Participants will be continuously monitored for safety and side effects. At the termination of the treatment, follow-up measurements will be taken.

The primary endpoint will be change in cerebral glucose metabolism, measured using 18F labeled fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET).

In addition to the registered outcome measures this pilot trial will explore the feasibility of acquiring data on the effect of sirolimus treatment on age-related tissue changes in the body using a variety of imaging modalities, such as bone mineral density assessed using quantitative computed tomography, retinal structures assessed using optical coherence tomography, periodontal tissue assessed using MRI and FDG-PET, cardiac function assessed using MRI, vessel wall in large arteries using MRI and [18F]FDG PET.

Conditions

Alzheimer Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Rapamycin

Sirolimus tablets will be administered orally, 7 mg once per week during 26 weeks

Group Type: EXPERIMENTAL

Sirolimus

Intervention Type: DRUG

7 mg taken once per week during 26 weeks.

Interventions

Sirolimus

7 mg taken once per week during 26 weeks.

Intervention Type: DRUG

Other Intervention Names

Rapamycin

Eligibility Criteria

Inclusion Criteria

1. Clinical diagnosis of mild cognitive impairment (MCI), or dementia of Alzheimer's type

2. Amyloid positivity established with either amyloid positron emission tomography or cerebrospinal fluid analysis.

3. For subjects with dementia, the disease should be in an early stage, operationalized as:

• Stage 4 (Mild dementia) or lower, according to the National Institute on Aging - Alzheimer's Association 2018 clinical staging criteria, AND
• Clinical Dementia Rating Scale (CDR) global score of 1 or lower, AND
• Montreal Cognitive Assessment (MoCA) score of ≥ 18 OR Rey Auditory Verbal Learning Test (RAVLT) >4 words after 30 minutes

4. Capable of giving, and has the capacity to give informed consent

5. Availability of a responsible study partner who can accompany the subject to all planned visits

6. Male or female between 50 and 80 years

7. Normal or clinically acceptable medical history, physical examination, and vital signs

Exclusion Criteria

1. History of any major disease that may interfere with safe engagement in the intervention (especially severe liver or kidney disease, or uncontrolled diabetes).

2. Central nervous system infarct, infection, or focal lesions of clinical significance on MRI scans.

3. Fulfills any contraindication for the use of sirolimus as per the summary of product characteristics, including but not restricted to:

• Current or planned medication with a strong inhibitor of CYP3A4 or P-gp
• Current or planned medication with a strong inducer of CYP3A4 or P-gp
• Other current medications with known serious interaction risks with sirolimus
• Known allergy or hypersensitivity to sirolimus

4. Significant obesity

5. Untreated and clinically significant hyperlipidemia

6. Treatment with immunosuppressive medications within the last 90 days (topical and nasal corticosteroids and inhaled corticosteroids for asthma are permitted), or chemotherapeutic agents for malignancy within the last 3 years

7. Major surgery within 3 months prior to the planned start of sirolimus treatment, OR has major surgery planned during the period of the trial.

8. Use of experimental medications for Alzheimer's or any other investigational medication or device within 60 days. Participants who have been involved in a monoclonal antibody study are excluded unless it is known that they were receiving placebo in that trial

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Karolinska University Hospital

OTHER

Sponsor Role: collaborator

Karolinska Institutet

OTHER

Sponsor Role: lead

Responsible Party

Jonas Svensson

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Pontus Plavén Sigray, PhD

Role: STUDY_DIRECTOR

Karolinska Institutet

Jonas Svensson, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Karolinska Institutet

Locations

Karolinska University Hospital Memory clinic

Solna, Stockholm County, Sweden

Countries

Sweden

References

Wallgren HA, Kivipelto M, Plaven-Sigray P, Svensson JE. Pharmacokinetic analysis of intermittent rapamycin administration in early-stage Alzheimer's Disease. Geroscience. 2025 Oct 5. doi: 10.1007/s11357-025-01911-3. Online ahead of print.

Reference Type: DERIVED

PMID: 41046300 (View on PubMed)

Svensson JE, Bolin M, Thor D, Williams PA, Brautaset R, Carlsson M, Sorensson P, Marlevi D, Spin-Neto R, Probst M, Hagman G, Moren AF, Kivipelto M, Plaven-Sigray P. Evaluating the effect of rapamycin treatment in Alzheimer's disease and aging using in vivo imaging: the ERAP phase IIa clinical study protocol. BMC Neurol. 2024 Apr 4;24(1):111. doi: 10.1186/s12883-024-03596-1.

Reference Type: DERIVED

PMID: 38575854 (View on PubMed)

Other Identifiers

2023-00611-01

Identifier Type: -

Identifier Source: org_study_id