Cognitive Impairment, MildPhase 2MCLENA-1NCT04032626
MCLENA-1: A Clinical Trial for the Assessment of Lenalidomide in Amnestic MCI Patients
A Phase 2 study testing Lenalidomide 10 mg in people with Cognitive Impairment, Mild and Cognitive Dysfunction, run by St. Joseph's Hospital and Medical Center, Phoenix at 2 sites in United States.
Trial summary
Accumulating evidence indicates that inflammation is prominent both in the blood and central nervous system (CNS) of Alzheimer's disease (AD) patients. These data suggest that systemic inflammation plays a crucial role in the cause and effects of AD neuropathology. Read more about this study
- Who is it for?
- Ages 50 to 89 years
- Conditions the study is for
- Cognitive Impairment, Mild, Cognitive Dysfunction, Amyloid Plaque
- What is being tested?
- Lenalidomide 10 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 2 sitesUnited States
- Study dates
- 22 Jul 2020to 31 May 2025
- Phase
- Phase 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 89 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- In order to be eligible for this study, subjects must meet the following inclusion criteria:
- Male or female outpatients.
- At least 50 years of age, but less than 90 (89 at time of screening).
- Females must be surgically sterile (bilateral tubal ligation, oophorectomy, or hysterectomy) or postmenopausal for 2 years (no women at risk of pregnancy will be accepted in this study).
- Must have been diagnosed with amnestic MCI based on the most recent NIA-AA criteria (Albert et al., 2011), i.e. at both the screening and baseline visits (visits 1 and 2) have a documented Mini Mental State Exam (MMSE) score between 22-28.
- CT or MRI scan of the brain obtained during the course of the dementia must be consistent with the diagnosis and show no evidence of significant focal lesions or of pathology which could contribute to dementia. If neither a CT nor an MRI scan is available from the past 12 months, a CT scan fulfilling the requirements must be obtained before randomization.
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- Vision and hearing must be sufficient to comply with study procedures.
- Be able to take oral medications.
- Hachinski ischemic score must be ≤ 4.
- Geriatric depression scale must be ≤ 10.
- Can be on stable doses of a cholinesterase inhibitor and/or memantine as long as it is stable for at least 90 days before the Baseline (Week 00) and is expected to remain on a stable dose for the remainder of the study period; or have demonstrated intolerance to or lack of efficacy from these medications.
- Must have a collateral informant/study partner who has significant direct contact with the patient at least 10 hours per week and who is willing to accompany the patient to all clinic visits and to be present during all telephone visits/interviews.
- If the patient has a legally authorized representative (LAR), the LAR must review and sign the informed consent form. If the patient does not have an LAR, the patient must appear able to provide informed consent and must review and sign the informed consent form. In addition, the patient's informant/study partner (as defined above) must sign the informed consent form. If the LAR and the patient's informant /study partner is the same individual, he/she should sign under both designations.
- Must be able to attend all study visits indicated in the schedule of visits.
- Patients with stable prostate cancer may be included at the discretion of the Medical Monitor.
- Medical records must document evidence of amnestic MCI with 1 of the following: MRI with hippocampal volume in the 5th percentile or lower for age, Amyloid PET positive at SUVr ≥ 1.05, CSF Tau profile with ATI lower than 1.0, FDG PET showing hypometabolism in the parietal temporal regions, or genetic confirmation of APOE4 (heterozygous or homozygous).
Who cannot join
- Subjects will be excluded if they have any of the condition listed below:
- Current evidence or history within the last 3 years of a neurological or psychiatric illness that could contribute to dementia, including (but not limited to) epilepsy, focal brain lesion, Parkinson's disease, seizure disorder, head injury with loss of consciousness
- DSM IV criteria for any major psychiatric disorder including psychosis, major depression and bipolar disorder.
- Known history or self-reported alcohol or substance abuse.
- Isolated living circumstances which would prohibit a study partner from providing sufficient and credible information about the participant.
- Poorly controlled hypertension.
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- History of myocardial infarction or signs or symptoms of unstable coronary artery disease within the last year (including revascularization procedure/angioplasty).
- Severe pulmonary disease (including chronic obstructive pulmonary disease) requiring more than 2 hospitalizations within the past year.
- Untreated sleep apnea.
- Any thyroid disease (unless euthyroid or on treatment for at least 6 months prior to screening).
- Active neoplastic disease (except for skin tumors other than melanoma). Patients with a history of prior malignancy are eligible provided they were treated with curative intent and (i) do not require any longer any active therapy; (ii) being considered in complete remission; and (iii) after the Medical Monitor's assessment/approval of each case.
- History of multiple myeloma.
- Absolute neutropenia of <750mm3, or history of neutropenia.
- History of or current thromboembolism (including deep venous thrombosis).
- Any clinically significant hepatic or renal disease (including presence of Hepatitis B or C antigen/antibody or an elevated transaminase levels of greater than two times the upper limit of normal (ULN) or creatinine greater than 1.5 x ULN).
- Clinically significant hematologic or coagulation disorder including any unexplained anemia or a platelet count less than 100,000/μL at screening.
- Use of any investigational drug within 30 days or within five half-lives of the investigational agent, whichever is longer.
- Use any investigational medical device within two weeks before screening or after end of the present study.
- Females who are at risk of pregnancy or are of child bearing age.
- Any other disease or condition that, in the opinion of the investigator, makes the patient unsuitable to participate in this clinical trial.
- Unwilling or unable to undergo MRI and PET imaging.
- Cardiac pacemaker or defibrillator or other implanted device.
- In the opinion of the Investigator, participation would not be in the best interest of the subject.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Cleveland Clinic Lou Ruvo Center for Brain health
Las Vegas, Nevada, 89103
St. Joseph's Hospital and Medical Center
Phoenix, Arizona, 85013
About this study
Official title: MCLENA-1: A Phase II Clinical Trial for the Assessment of Safety, Tolerability, and Efficacy of Lenalidomide in Patients With Mild Cognitive Impairment Due to Alzheimer's Disease
Accumulating evidence indicates that inflammation is prominent both in the blood and central nervous system (CNS) of Alzheimer's disease (AD) patients. These data suggest that systemic inflammation plays a crucial role in the cause and effects of AD neuropathology. Capitalizing on the experience from a previous clinical trial with thalidomide, here, the investigators hypothesize that modulating both systemic and CNS inflammation via the pleiotropic immunomodulator lenalidomide is a putative therapeutic intervention for AD if administered at a proper time window during the course of the disease.
Read the detailed description
There are currently no approved treatments to treat the neuroinflammatory aspects of AD. While inflammation is pervasive to many neurological disorders, no clinical trial has yet demonstrated the efficacy of anti-inflammatory agents for AD. Interestingly, chronic peripheral low-grade inflammation is associated with aging and increases the risk for disease and mortality, including AD. Accumulating evidence indicates that nuclear factor-kappa B, tumor necrosis factor alpha (TNFα), interleukins (e.g. IL-1beta, IL-2, and IL-6), and chemokines (e.g. IL-8) are found elevated both in the blood and central nervous system (CNS) of AD patients. These data confirm that inflammation plays a central role in the cause and effect of AD neuropathology.
The immunomodulator, anti-cancer agent lenalidomide is one of the very few pleiotropic agents that both lowers the expression of TNFα, IL-6, IL-8, and increases the expression of anti-inflammatory cytokines (e.g. IL-10), to modulate both innate and adaptive immune responses.
In the current project the investigators aim to test the central hypothesis that lenalidomide reduces inflammatory and AD-associated pathological biomarkers, and improves cognition. For this, the investigators designed an 18-month, Phase II, double-blind, randomized, two-armed, parallel group, placebo controlled, and proof-of-mechanism clinical study in early symptomatic AD subjects (i.e. amnestic mild cognitive impairment; aMCI). The effects of lenalidomide treatment will be assessed after 12 months of treatment and 6 months washout (month 18).
- Conditions
- Cognitive Impairment, Mild, Cognitive Dysfunction, Amyloid Plaque, Neurodegeneration, Inflammation, Brain
- Being tested
- Lenalidomide 10 mg, Placebo
- Keywords
- Alzheimer's disease, Biomarkers, Brain Amyloid, Brain Imaging, Cognition, Immunomodulation
- Medical subject headings
- Cognitive Dysfunction, Plaque, Amyloid, Nerve Degeneration, Encephalitis, Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lenalidomide 10 mgDrug
Also called Lenalid
Lenalid
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Lenalidomide | Experimental | Lenalidomide 10 mg/day taken daily orally for 12 months of treatment followed by 6 months washout. The trial will last 18 month in duration. Receives: Drug: Lenalidomide 10 mg |
| Placebo | Placebo comparator | Placebo taken daily orally for 12 months of treatment followed by 6 months washout. The trial will last 18 month in duration. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in cognition as assessed by the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) total score
To evaluate the effect on cognition Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) of lenalidomide 10 mg/kg titrated for up to 12 months and washed out for 6 months. ADAS is 70 points. A lower score is better
Measured: 18 months
Change in cognition as assessed by the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) total score
To evaluate the effect on cognitionAlzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) of lenalidomide 10 mg/kg titrated for up to 12 months and washed out for 6 months. The maximum score is 30. A higher score is better
Measured: 18 months
Change in cognition as assessed by the Clinical Dementia Rating - Sum of Boxes (CDR-SOB) total score
To evaluate the effect on cognition Clinical Dementia Rating - Sum of Boxes (CDR-SOB) of lenalidomide 10 mg/kg titrated for up to 12 months and washed out for 6 months. The SOB maximum total is 18. A lower score is better
Measured: 18 months
Change in cognition as assessed by the Mini Mental State Examination (MMSE) total score
To evaluate the effect on cognition Mini Mental State Examination (MMSE) of lenalidomide 10 mg/kg titrated for up to 12 months and washed out for 6 months. The maximum score is 30. A higher score is better
Measured: 18 months
Secondary outcomes (1)
Monitoring and recording of all adverse events (AEs) and serious adverse events (SAEs)
To evaluate the safety and tolerability of lenalidomide 10 mg/kg titrated for up to 12 months and washed out for 6 months. Particularly, we will monitor blood toxicities reported in oncology studies. Blood toxicity will be defined as platelets falling below 50,000/μL and/or neutrophils falling below 1,000/μL.
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2019
- Study start22 Jul 2020
- Primary completion31 May 2025
- Study completion31 May 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cognitive Impairment, MildStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This study will take place at a single site. We will enroll 30 male and female outpatients, 50-90 years of age. Lenalidomide 10 mg/day vs. placebo will be taken daily orally (ratio 1:1). The effects of lenalidomide treatment will be assessed after 12 months of treatment and 6 months washout (month 18). Participants completing the study will be involved for up to 20 months in duration, from screening to end of study.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Joseph's Hospital and Medical Center, Phoenix
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA), The Cleveland Clinic
- Responsible party
- Principal investigator, Marwan Sabbagh, St. Joseph's Hospital and Medical Center, Phoenix
- Investigators
- Marwan N Sabbagh, M.D., Principal investigator, St. Joseph's Hospital and Medical Center, PhoenixBoris Decourt, PhD, Study chair, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04032626
- Sponsor's protocol ID
- 19-658
- Other IDs
- R01AG059008, K01AG047279
- Acronym
- MCLENA-1
- Status last verified
- May 2026
- First submitted
- 10 Jul 2019
- Last updated
- 10 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The protocol used and data collected in the course of this study will be shared with other researchers. The protocol will be published in a scientific journal and presented as posters in scientific meetings. Data and remaining biosamples, after deidentification, will be made available to the community 6 months after publication of the results of the study in peer-reviewed articles.
Study at a glance
From the registry record, last updated by the sponsor on 10 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MCLENA-1: A Phase II Clinical Trial for the Assessment of Safety, Tolerability, and Efficacy of Lenalidomide in Patients With Mild Cognitive Impairment Due to Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT04032626
- Acronym / sponsor ID
- MCLENA-1 / 19-658
- Conditions
- Cognitive Impairment, Mild, Cognitive Dysfunction, Amyloid Plaque, Neurodegeneration, Inflammation, Brain
- Keywords
- Alzheimer's disease, Biomarkers, Brain Amyloid, Brain Imaging, Cognition, Immunomodulation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- St. Joseph's Hospital and Medical Center, PhoenixUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA), The Cleveland Clinic
- Study start
- 22 Jul 2020 (actual)
- Primary completion
- 31 May 2025 (actual)
- Study completion
- 31 May 2025 (actual)
- First posted
- 25 Jul 2019 (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.
Accumulating evidence indicates that inflammation is prominent both in the blood and central nervous system (CNS) of Alzheimer's disease (AD) patients. These data suggest that systemic inflammation plays a crucial role in the cause and effects of AD neuropathology. Capitalizing on the experience from a previous clinical trial with thalidomide, here, the investigators hypothesize that modulating both systemic and CNS inflammation via the pleiotropic immunomodulator lenalidomide is a putative therapeutic intervention for AD if administered at a proper time window during the course of the disease.
Detailed description
There are currently no approved treatments to treat the neuroinflammatory aspects of AD. While inflammation is pervasive to many neurological disorders, no clinical trial has yet demonstrated the efficacy of anti-inflammatory agents for AD. Interestingly, chronic peripheral low-grade inflammation is associated with aging and increases the risk for disease and mortality, including AD. Accumulating evidence indicates that nuclear factor-kappa B, tumor necrosis factor alpha (TNFα), interleukins (e.g. IL-1beta, IL-2, and IL-6), and chemokines (e.g. IL-8) are found elevated both in the blood and central nervous system (CNS) of AD patients. These data confirm that inflammation plays a central role in the cause and effect of AD neuropathology.
The immunomodulator, anti-cancer agent lenalidomide is one of the very few pleiotropic agents that both lowers the expression of TNFα, IL-6, IL-8, and increases the expression of anti-inflammatory cytokines (e.g. IL-10), to modulate both innate and adaptive immune responses.
In the current project the investigators aim to test the central hypothesis that lenalidomide reduces inflammatory and AD-associated pathological biomarkers, and improves cognition. For this, the investigators designed an 18-month, Phase II, double-blind, randomized, two-armed, parallel group, placebo controlled, and proof-of-mechanism clinical study in early symptomatic AD subjects (i.e. amnestic mild cognitive impairment; aMCI). The effects of lenalidomide treatment will be assessed after 12 months of treatment and 6 months washout (month 18).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- This study will take place at a single site. We will enroll 30 male and female outpatients, 50-90 years of age. Lenalidomide 10 mg/day vs. placebo will be taken daily orally (ratio 1:1). The effects of lenalidomide treatment will be assessed after 12 months of treatment and 6 months washout (month 18). Participants completing the study will be involved for up to 20 months in duration, from screening to end of study.
| Arm | Type | Receives |
|---|---|---|
| Lenalidomide | Experimental | Drug: Lenalidomide 10 mgLenalidomide 10 mg/day taken daily orally for 12 months of treatment followed by 6 months washout. The trial will last 18 month in duration. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo taken daily orally for 12 months of treatment followed by 6 months washout. The trial will last 18 month in duration. |
Who may qualify
- Ages
- 50 to 89 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- In order to be eligible for this study, subjects must meet the following inclusion criteria:
Key exclusion criteria (23 listed)
- Subjects will be excluded if they have any of the condition listed below:
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 |
|---|---|---|
| Lenalidomide 10 mgAlso: LenalidLenalid | Drug | Lenalidomide |
| PlaceboPlacebo | Drug | Placebo |
Primary outcome
Change in cognition as assessed by the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) total score
Time frame: 18 months
To evaluate the effect on cognition Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) of lenalidomide 10 mg/kg titrated for up to 12 months and washed out for 6 months. ADAS is 70 points. A lower score is better
Change in cognition as assessed by the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) total score
Time frame: 18 months
To evaluate the effect on cognitionAlzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) of lenalidomide 10 mg/kg titrated for up to 12 months and washed out for 6 months. The maximum score is 30. A higher score is better
Change in cognition as assessed by the Clinical Dementia Rating - Sum of Boxes (CDR-SOB) total score
Time frame: 18 months
To evaluate the effect on cognition Clinical Dementia Rating - Sum of Boxes (CDR-SOB) of lenalidomide 10 mg/kg titrated for up to 12 months and washed out for 6 months. The SOB maximum total is 18. A lower score is better
Change in cognition as assessed by the Mini Mental State Examination (MMSE) total score
Time frame: 18 months
To evaluate the effect on cognition Mini Mental State Examination (MMSE) of lenalidomide 10 mg/kg titrated for up to 12 months and washed out for 6 months. The maximum score is 30. A higher score is better
1 secondary outcome
Monitoring and recording of all adverse events (AEs) and serious adverse events (SAEs)
Time frame: 18 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 10 Jun 2026.
- Individual participant dataSharing planned: Yes. The protocol used and data collected in the course of this study will be shared with other researchers. The protocol will be published in a scientific journal and presented as posters in scientific meetings. Data and remaining biosamples, after deidentification, will be made available to the community 6 months after publication of the results of the study in peer-reviewed articles.
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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.
Marwan N Sabbagh, M.D. principal investigator
St. Joseph's Hospital and Medical Center, Phoenix
Boris Decourt, PhD study chair
The Cleveland Clinic
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lenalidomide 10 mg in people with Cognitive Impairment, Mild and Cognitive Dysfunction, run by St. Joseph's Hospital and Medical Center, Phoenix at 2 sites in United States.
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 16 inclusion and 23 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 10 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
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 cognition as assessed by the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) total score (time frame: 18 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Jun 2026.