Cognitive Impairment, MildPhase 2NCT06177028
MCLENA-2: A Phase II Clinical Trial for the Assessment of Lenalidomide in Patients With Mild Cognitive Impairment
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.
Trial summary
This is a randomized, double-blind, placebo-controlled, parallel group study. The use of placebo is appropriate to minimize bias related to treatment expectations of the subject, study partner, and site investigator, as well as to changes in the relationship between the subject and study partner that might occur with… Read more about this study
- Who is it for?
- Ages 50 to 90 yearsHealthy volunteers can take part
- 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
- 45 participants
- Where
- No sites listed yet
- Study dates
- 1 Jun 2025to 2 Jan 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 90 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
- Vision and hearing must be sufficient to comply with study procedures.
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- 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 screening 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 specified clinic visits, supervise administration of all study medication, and be available for 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 an 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 reside in the community.
- Patients with stable prostate cancer may be included at the discretion of the Medical Monitor.
- Positivity for amyloid brain scan: Amyloid PET positive at SUVr of 1.05
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.
- Unwilling or unable to undergo a Lumbar Puncture.
- Known history or self-reported alcohol or substance abuse.
- Living alone.
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- Poorly controlled hypertension. 7 .History of myocardial infarction or signs or symptoms of unstable coronary artery disease within the last year (including revascularization procedure/angioplasty).
- 8. Severe pulmonary disease (including chronic obstructive pulmonary disease) requiring more than 2 hospitalizations within the past year.
- 9. Untreated sleep apnea. 10. Any thyroid disease (unless euthyroid on treatment for at least 6 months prior to screening).
- 11. Active neoplastic disease (except for skin tumors other than melanoma) within five years.
- 12. History of multiple myeloma. 13. Absolute neutropenia of <750/mm3, or a history of neutropenia. 14. History of or current thromboembolism (including deep venous thrombosis). 15. 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).
- 16. Clinically significant hematologic or coagulation disorder including any unexplained anemia or a platelet count less than 100,000/μL at screening.
- 17. Use of any investigational drug within 30 days or within five half-lives of the investigational agent, whichever is longer.
- 18. Use any investigational medical device within two weeks before screening or after end of the present study.
- 19. Females who are at risk of pregnancy or are of child bearing age. 20. Unwilling or unable to undergo MRI and PET imaging. 21. Cardiac pacemaker or defibrillator or other implanted device. 22. In the opinion of the investigator, participation would not be in the best interest of the subject
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: MCLENA-2: A Phase II Clinical Trial for the Assessment of Biomarker Trajectory in Patients With Mild Cognitive Impairment Due to Alzheimer's Disease Treated With Lenalidomide (Amendment to IND # 142121)
This is a randomized, double-blind, placebo-controlled, parallel group study. The use of placebo is appropriate to minimize bias related to treatment expectations of the subject, study partner, and site investigator, as well as to changes in the relationship between the subject and study partner that might occur with the initiation of treatment and expectation of improvement in motor symptoms or cognition. Changes in subject/study partner interactions can impact subject mood and might introduce biases that cannot be quantified. The double-blind use of placebo will also prevent bias in the clinical and scientific assessments.
Read the detailed description
There are currently no FDA-approved medications indicated for the treatment 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 we aim to test the central hypothesis that lenalidomide reduces inflammatory and AD-associated pathological biomarkers in the blood and CSF. For this, we designed a 6-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 continuously for 26 weeks and 4 weeks washout (total of 30 weeks).
- Conditions
- Cognitive Impairment, Mild, Cognitive Dysfunction, Amyloid Plaque, Neurodegenerative Disease, Hereditary, Inflammation, Brain
- Being tested
- Lenalidomide 10 mg
- Keywords
- Alzheimer's disease, CSF, Biomarkers, Brain Imaging, Brain Amyloid, Memory Loss, Immunomodulation
- Medical subject headings
- Cognitive Dysfunction, Plaque, Amyloid, Heredodegenerative Disorders, Nervous System, Encephalitis, Alzheimer Disease, Memory Disorders
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
Lenalidomide is a cancer drug, It is also known by it's brand name Revlimid.
| Study group | Role | What they receive |
|---|---|---|
| Lenalidomide | Experimental | Lenalidomide 10 mg/day taken daily orally for 26 weeks of treatment followed by 4 weeks of washout. The trial will last up to 30 weeks in duration. Receives: Drug: Lenalidomide 10 mg |
| Placebo | Placebo comparator | Placebo taken daily orally for 26 weeks of treatment followed by 4 weeks of washout. The trial will last up to 30 weeks in duration. Receives: Drug: Lenalidomide 10 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the effect of lenalidomide
To assess the effect of lenalidomide on inflammatory markers in CSF and blood, as well as safety and toxicity.
Measured: After 26 weeks of treatment
Secondary outcomes (1)
To asses the effect of lenalidomide
: To assess the effects of lenalidomide on CSF makers of AD (e.g. amyloid beta and tau levels) in aMCI patients
Measured: 26 weeks of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2023
- Study start1 Jun 2025 (estimated)
- Primary completion2 Jan 2026 (estimated)
- Study completion2 Jan 2027 (estimated)
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 45 male and female participants, 50-90 years of age, in general good health, with mild cognitive impairment due to AD. The trial will last up to 30 weeks in duration. Lenalidomide 10 mg/day vs. placebo taken daily orally (ratio 2:1). Participants completing the study will be involved for up to 45 weeks in duration, from screening to end of the study.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- St. Joseph's Hospital and Medical Center, Phoenix
- Sponsor type
- University, hospital or other
- Collaborators
- Texas Tech University
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06177028
- Sponsor's protocol ID
- 2013717
- Status last verified
- May 2025
- First submitted
- 11 Dec 2023
- Last updated
- 18 May 2025
- 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 bio samples, 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 18 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MCLENA-2: A Phase II Clinical Trial for the Assessment of Biomarker Trajectory in Patients With Mild Cognitive Impairment Due to Alzheimer's Disease Treated With Lenalidomide (Amendment to IND # 142121)
- ClinicalTrials.gov ID
- NCT06177028
- Acronym / sponsor ID
- 2013717
- Conditions
- Cognitive Impairment, Mild, Cognitive Dysfunction, Amyloid Plaque, Neurodegenerative Disease, Hereditary, Inflammation, Brain
- Keywords
- Alzheimer's disease, CSF, Biomarkers, Brain Imaging, Brain Amyloid, Memory Loss, Immunomodulation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- St. Joseph's Hospital and Medical Center, PhoenixUniversity, hospital or other
- Collaborators
- Texas Tech University
- Study start
- 1 Jun 2025 (estimated)
- Primary completion
- 2 Jan 2026 (estimated)
- Study completion
- 2 Jan 2027 (estimated)
- First posted
- 20 Dec 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 is a randomized, double-blind, placebo-controlled, parallel group study. The use of placebo is appropriate to minimize bias related to treatment expectations of the subject, study partner, and site investigator, as well as to changes in the relationship between the subject and study partner that might occur with the initiation of treatment and expectation of improvement in motor symptoms or cognition. Changes in subject/study partner interactions can impact subject mood and might introduce biases that cannot be quantified. The double-blind use of placebo will also prevent bias in the clinical and scientific assessments.
Detailed description
There are currently no FDA-approved medications indicated for the treatment 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 we aim to test the central hypothesis that lenalidomide reduces inflammatory and AD-associated pathological biomarkers in the blood and CSF. For this, we designed a 6-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 continuously for 26 weeks and 4 weeks washout (total of 30 weeks).
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 45 male and female participants, 50-90 years of age, in general good health, with mild cognitive impairment due to AD. The trial will last up to 30 weeks in duration. Lenalidomide 10 mg/day vs. placebo taken daily orally (ratio 2:1). Participants completing the study will be involved for up to 45 weeks in duration, from screening to end of the study.
| Arm | Type | Receives |
|---|---|---|
| Lenalidomide | Experimental | Drug: Lenalidomide 10 mgLenalidomide 10 mg/day taken daily orally for 26 weeks of treatment followed by 4 weeks of washout. The trial will last up to 30 weeks in duration. |
| Placebo | Placebo comparator | Drug: Lenalidomide 10 mgPlacebo taken daily orally for 26 weeks of treatment followed by 4 weeks of washout. The trial will last up to 30 weeks in duration. |
Who may qualify
- Ages
- 50 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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.
Key exclusion criteria (15 listed)
- 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.
- Unwilling or unable to undergo a Lumbar Puncture.
- Known history or self-reported alcohol or substance abuse.
- Living alone.
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: LenalidLenalidomide is a cancer drug, It is also known by it's brand name Revlimid. | Drug | Lenalidomide, Placebo |
Primary outcome
To assess the effect of lenalidomide
Time frame: After 26 weeks of treatment
To assess the effect of lenalidomide on inflammatory markers in CSF and blood, as well as safety and toxicity.
1 secondary outcome
To asses the effect of lenalidomide
Time frame: 26 weeks of treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2025.
- 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 bio samples, 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.
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.
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 15 inclusion and 15 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: opening soon, as of the sponsor's last update on 18 May 2025. Status can change between updates, so confirm with the study contact before making plans.
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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Marwan N Sabbagh, M.D (602-406-7735, Marwan.Sabbagh@commonspirit.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To assess the effect of lenalidomide (time frame: After 26 weeks of treatment). 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 18 May 2025.