Alzheimer DiseasePhase 1/2ERAPNCT06022068
Evaluating Rapamycin Treatment in Alzheimer's Disease Using Positron Emission Tomography
A Phase 1/2 study testing Sirolimus in people with Alzheimer Disease, run by Karolinska Institutet at 1 site in Sweden.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 to 80 years
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- Sirolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteSweden
- Study dates
- 1 Sep 2023to 17 Jan 2025
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
Sweden1 site
Karolinska University Hospital Memory clinic
Solna, Stockholm County, 171 64
About this study
Official title: Evaluating Rapamycin Treatment in Alzheimer's Disease Using Positron Emission Tomography (ERAP)
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.
Read more
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
- Being tested
- Sirolimus
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SirolimusDrug
Also called Rapamycin
7 mg taken once per week during 26 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Rapamycin | Experimental | Sirolimus tablets will be administered orally, 7 mg once per week during 26 weeks Receives: Drug: Sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in cerebral glucose metabolism
Cerebral glucose uptake measured through [18F]FDG positron emission tomography
Measured: From baseline to six months
Secondary outcomes (9)
Incidence of Treatment-Emergent Adverse Events
Safety and tolerability of intermittent sirolimus treatment
Measured: From baseline to six months
Change in Cerebrospinal fluid (CSF) concentration of amyloid beta 42
CSF biomarker for Alzheimers disease
Measured: From baseline to six months
Change in CSF concentration of phosphorylated tau
CSF biomarker for Alzheimers disease
Measured: From baseline to six months
Change in CSF concentration of total tau
CSF biomarker for Alzheimers disease
Measured: From baseline to six months
Change in cerebral blood flow
Cerebral blood flow measured with MRI using arterial spin labeling
Measured: From baseline to six months
Area under the concentration versus time curve (AUC) of sirolimus
Whole blood measurements of sirolimus concentration.
Measured: Tested at one occasion between baseline to six months
Peak Plasma Concentration (Cmax) of sirolimus
Whole blood measurements of sirolimus concentration.
Measured: Tested at one occasion between baseline to six months
Trough Plasma Concentration (Cmin) of sirolimus
Whole blood measurements of sirolimus concentration.
Measured: Tested at one occasion between baseline to six months
Change in Montreal Cognitive Assessment (MoCA) rating
Cognition assessed using the MoCA rating scale (0-30 points, higher scores indicating better cognitive performance)
Measured: From baseline to six months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2023
- Study start1 Sep 2023
- Primary completion11 Dec 2024
- Study completion17 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by Karolinska InstitutetThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Karolinska Institutet
- Sponsor type
- University, hospital or other
- Collaborators
- Karolinska University Hospital
- Responsible party
- Principal investigator, Jonas Svensson, Karolinska Institutet
- Investigators
- Pontus Plavén Sigray, PhD, Study director, Karolinska InstitutetJonas Svensson, MD, PhD, Principal investigator, Karolinska Institutet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06022068
- Sponsor's protocol ID
- 2023-00611-01
- Other IDs
- 2023
- Acronym
- ERAP
- Status last verified
- Jun 2025
- First submitted
- 15 Aug 2023
- Last updated
- 3 Jul 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: We aim to share pseudonymized individual participant data that underlie results in a publication in accordance with institutional regulations.
Publications
Wallgren HA, Kivipelto M, Plaven-Sigray P, Svensson JE. Pharmacokinetic analysis of intermittent rapamycin administration in early-stage Alzheimer's Disease. Geroscience. 2026 Jun;48(3):3295-3304. doi: 10.1007/s11357-025-01911-3. Epub 2025 Oct 5.
PubMed 41046300Svensson 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.
PubMed 38575854
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating Rapamycin Treatment in Alzheimer's Disease Using Positron Emission Tomography (ERAP)
- ClinicalTrials.gov ID
- NCT06022068
- Acronym / sponsor ID
- ERAP / 2023-00611-01
- Conditions
- Alzheimer Disease
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Karolinska InstitutetUniversity, hospital or other
- Collaborators
- Karolinska University Hospital
- Study start
- 1 Sep 2023 (actual)
- Primary completion
- 11 Dec 2024 (actual)
- Study completion
- 17 Jan 2025 (actual)
- First posted
- 1 Sep 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Rapamycin | Experimental | Drug: SirolimusSirolimus tablets will be administered orally, 7 mg once per week during 26 weeks |
Who may qualify
- Ages
- 50 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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:
- 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
Key exclusion criteria (12 listed)
- 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:
- Significant obesity
- Untreated and clinically significant hyperlipidemia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SirolimusAlso: Rapamycin7 mg taken once per week during 26 weeks. | Drug | Rapamycin |
Primary outcome
Change in cerebral glucose metabolism
Time frame: From baseline to six months
Cerebral glucose uptake measured through [18F]FDG positron emission tomography
9 secondary outcomes
Incidence of Treatment-Emergent Adverse Events
Time frame: From baseline to six months
Change in Cerebrospinal fluid (CSF) concentration of amyloid beta 42
Time frame: From baseline to six months
Change in CSF concentration of phosphorylated tau
Time frame: From baseline to six months
Change in CSF concentration of total tau
Time frame: From baseline to six months
Change in cerebral blood flow
Time frame: From baseline to six months
Area under the concentration versus time curve (AUC) of sirolimus
Time frame: Tested at one occasion between baseline to six months
Peak Plasma Concentration (Cmax) of sirolimus
Time frame: Tested at one occasion between baseline to six months
Trough Plasma Concentration (Cmin) of sirolimus
Time frame: Tested at one occasion between baseline to six months
Change in Montreal Cognitive Assessment (MoCA) rating
Time frame: From baseline to six months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2025.
- Derived from this study: PubMed 41046300Wallgren HA, Kivipelto M, Plaven-Sigray P, Svensson JE. Pharmacokinetic analysis of intermittent rapamycin administration in early-stage Alzheimer's Disease. Geroscience. 2026 Jun;48(3):3295-3304. doi: 10.1007/s11357-025-01911-3. Epub 2025 Oct 5.
- Derived from this study: PubMed 38575854Svensson 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.
- Individual participant dataSharing planned: Undecided. We aim to share pseudonymized individual participant data that underlie results in a publication in accordance with institutional regulations.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pontus Plavén Sigray, PhD study director
Karolinska Institutet
Jonas Svensson, MD, PhD principal investigator
Karolinska Institutet
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Sirolimus in people with Alzheimer Disease, run by Karolinska Institutet at 1 site in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in cerebral glucose metabolism (time frame: From baseline to six months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06022068, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jul 2025.