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

NCT06022068 | Completed Phase 1 DMC

• 1 other identifier: 2023-00611-01
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Change in cerebral glucose metabolism

  Cerebral glucose uptake measured through \[18F\]FDG positron emission tomography

  From baseline to six months

Secondary Outcomes (9)

• Incidence of Treatment-Emergent Adverse Events

  From baseline to six months

• Change in Cerebrospinal fluid (CSF) concentration of amyloid beta 42

  From baseline to six months

• Change in CSF concentration of phosphorylated tau

  From baseline to six months

• Change in CSF concentration of total tau

  From baseline to six months

• Change in cerebral blood flow

  From baseline to six months

Other Outcomes (7)

• Change in composite z-score of neuropsychological tests

  From baseline to six months

• Change in concentration of neurofilament light in CSF

  From baseline to six months

• Change in quotient of albumin concentration in serum and CSF

  From baseline to six months

Study Arms (1)

Rapamycin

EXPERIMENTAL

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

Drug: Sirolimus

Interventions

Sirolimus DRUG

7 mg taken once per week during 26 weeks.

Also known as: Rapamycin

Rapamycin

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical diagnosis of mild cognitive impairment (MCI), or dementia of Alzheimer's type
• Amyloid positivity established with either amyloid positron emission tomography or cerebrospinal fluid analysis.
• 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
• Capable of giving, and has the capacity to give informed consent
• Availability of a responsible study partner who can accompany the subject to all planned visits
• Male or female between 50 and 80 years
• Normal or clinically acceptable medical history, physical examination, and vital signs

You may not qualify if:

• History of any major disease that may interfere with safe engagement in the intervention (especially severe liver or kidney disease, or uncontrolled diabetes).
• Central nervous system infarct, infection, or focal lesions of clinical significance on MRI scans.
• 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
• Significant obesity
• Untreated and clinically significant hyperlipidemia
• 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
• Major surgery within 3 months prior to the planned start of sirolimus treatment, OR has major surgery planned during the period of the trial.
• 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

Sponsors & Collaborators

• Karolinska Institutet: lead
• Karolinska University Hospital: collaborator

Study Sites (1)

Karolinska University Hospital Memory clinic

Solna, Stockholm County, 171 64, Sweden

Location

Related Publications (2)

• 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.

  PMID: 41046300 DERIVED

• 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.

  PMID: 38575854 DERIVED

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Pontus Plavén Sigray, PhD

  Karolinska Institutet

  STUDY DIRECTOR

• Jonas Svensson, MD, PhD

  Karolinska Institutet

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: August 15, 2023
• First Posted: September 1, 2023
• Study Start: September 1, 2023
• Primary Completion: December 11, 2024
• Study Completion: January 17, 2025
• Last Updated: July 3, 2025

Record last verified: 2025-06

Locations

SE (1)