Alzheimer DiseasePhase 2NCT03991988
Montelukast Therapy on Alzheimer's Disease
A Phase 2 study testing Montelukast in people with Alzheimer Disease, run by Emory University at 4 sites in United States.
Trial summary
This is a one-year, double-blind placebo-controlled randomized clinical trial that compares montelukast to placebo in individuals with mild cognitive impairment (MCI) and early Alzheimer's disease (AD) dementia. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- Montelukast
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 4 sitesUnited States
- Study dates
- 25 Sep 2019to 18 Nov 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age: 50 years or older
- MCI group will be defined based on:
- Subjective memory concern;
- Abnormal memory function documented using the Logical Memory subscale (Delayed Paragraph Recall, Paragraph A only) from the Wechsler Memory Scale-Revised (the maximum score is 25): [<11 for 16 or more years of education; <9 for 8-15 years of education; <6 for <7 years of education];
- Montreal Cognitive Assessment (MoCA) < 26;
- Clinical Dementia Rating (CDR) scale /Memory box score=0.5;
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- General functional performance sufficiently preserved (Functional Assessment Questionnaire ≤5).
- Early AD dementia group will be defined based on:
- Subjective memory concern;
- Abnormal memory function documented using the Logical Memory subscale (Delayed Paragraph Recall, Paragraph A only) from the Wechsler Memory Scale-Revised (the maximum score is 25): [<11 for 16 or more years of education; <9 for 8-15 years of education; <6 for <7 years of education];
- Montreal Cognitive Assessment (MoCA) <26;
- Clinical Dementia Rating scale/Memory box score 1 or 2;
- Early AD dementia defined as Functional Assessment Staging Test (FAST) of 4 or 5
Who cannot join
- Intolerance to Montelukast;
- Current diagnosis of bronchial asthma or exercise-induced bronchospasm and currently on Montelukast or other leukotriene receptor antagonists (Zafirlukast, Pranlukast);
- Liver disease (elevated liver enzymes (>2x normal): Alanine aminotransferase (ALT), AST, alkaline phosphatase, total bilirubin);
- Renal disease (Creatinine >2.0 mg/dl), platelets<50,000/μl, or INR>1.9;
- Diagnosis of any neurological or psychiatric disorders that affects cognition such as uncontrolled depression, schizophrenia, Parkinson's disease or use of anti-Parkinsonian therapies (unless used for essential tremor), multiple sclerosis, or other active medical condition that in the judgment of the study physicians would affect the safety of the subject or scientific integrity of the study;
- Other contributing factors to cognitive impairment such as uncontrolled hypothyroidism (TSH >10 mU/l) or untreated low vitamin B12 (<250 ng/mL);
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- Uncontrolled congestive heart failure reflected by poor exercise tolerance and shortness of breath at rest or with some exertion;
- Actively undergoing chemotherapy or radiation therapy for cancer treatment;
- History of stroke in the past 3 years;
- Severely impaired cognition (MoCA ≤10, FAST >5 or CDR >2);
- Inability to have MRI and LP e.g. for MRI, metal implants or cardiac pacemaker or for LP, bleeding diathesis from disease states or from use of anticoagulants such as warfarin, heparin and related products, Rivaroxaban or Xarelto, Apixaban or Eliquis, Edoxaban or Savaysa, Dabigatran or Pradaxa. Subjects who can have either one lumbar puncture (LP) or MRI will be enrolled;
- Inability to have cognitive assessment due to hearing, vision, or language issues or due to severe impairment;
- History of increased intracranial pressure (ICP);
- In those who are unable to demonstrate that they understood the details of the study using the University of California, San Diego Brief Assessment of Capacity to Consent (UBACC) instrument modified for EMERALD (i.e. lack of decisional-capacity to consent), a study partner/surrogate who can sign on their behalf will be required; otherwise, they will be excluded;
- Use of phenobarbital or rifampin due to drug interaction.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Emory Clinic
Atlanta, Georgia, 30322
Emory University Hospital Clinical Research Network
Atlanta, Georgia, 30322
Executive Park
Atlanta, Georgia, 30329
Wesley Woods
Atlanta, Georgia, 30329
About this study
Official title: Effects of Montelukast Therapy on Alzheimer's Disease (EMERALD)
This is a one-year, double-blind placebo-controlled randomized clinical trial that compares montelukast to placebo in individuals with mild cognitive impairment (MCI) and early Alzheimer's disease (AD) dementia. The measures include cognitive function, cerebrospinal fluid (CSF) biomarkers and neuroimaging (cerebral perfusion and markers of vascular brain damage).
Participants will be treated with montelukast (escalating doses:10, 20 to 40 mg) or matched placebo.
Read the detailed description
Treatment options for Alzheimer's disease (AD) remain limited, especially treatments linking neurovascular and neuroinflammatory changes with clinical manifestations of the disease. Prior research studies have documented a positive effect of cysteinyl leukotriene type 1 (cysLT-1) receptor antagonist, particularly Montelukast, on inflammatory processes in the brain and on neuronal injury, blood-brain-barrier (BBB) integrity, and amyloid-β42 (Aβ) protein accumulation. Although montelukast is currently in use for the treatment of inflammatory diseases e.g. bronchial asthma and exercise-induced bronchospasm, its effects on memory and thinking abilities and on AD biomarkers are yet to be fully understood.
This is a single site randomized controlled trial at Emory University that compares the effects of montelukast vs. placebo on memory and thinking abilities, as well as on brain imaging and markers of brain degeneration. Each participant will undergo a screening process following informed consent to determine if they meet study eligibility criteria. Participants will be enrolled in the study for 1 year.
- Conditions
- Alzheimer Disease
- Being tested
- Montelukast, Placebo oral tablet
- Keywords
- Alzheimer
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MontelukastDrug
Participants in this arm will take a pill of Montelukast daily on escalating doses: 10, 20 to 40 mg.
All participants will be initiated on 10 mg. The dose will be increased in 2-week increments to 20 mg and 40 mg as long as participants report no intolerable symptoms or adverse events.
Placebo oral tabletDrug
Participants in this arm will take a matched placebo pill daily
| Study group | Role | What they receive |
|---|---|---|
| Montelukast Group | Experimental | Montelukast (10, 20, or 40 mg) Receives: Drug: Montelukast |
| Placebo Group | Placebo comparator | Matched placebo pill Receives: Drug: Placebo oral tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Any Gastrointestinal (GI) Symptoms
Number of participants with any GI symptoms reported: diarrhea, nausea, vomiting
Measured: Baseline, 1 year
Number of Participants With Reported Anaphylaxis
Number of participants with reported anaphylaxis during follow up time
Measured: Baseline, 1 year
Number of Participants With Elevated Liver Enzymes
Number of participants with elevated liver enzymes during follow up
Measured: Baseline, 1 year
Prothrombin Time (PT)/ International Normalized Ratio (INR)
Prothrombin time (PT)/ international normalized ratio (INR) will be measured at baseline and 1 year.
Measured: Baseline, 1 year
Neuropsychiatric Inventory Questionnaire (NPI-Q) Score
The NPI-Q is designed to be a self-administered questionnaire completed by informants about patients for whom they care. Each of the 12 NPI-Q domains contains a survey question that reflects cardinal symptoms of that domain. Initial responses to each domain question are "Yes" (present) or "No" (absent). If the response to the domain question is "No", the informant goes to the next question. If "Yes", the informant then rates both the Severity of the symptoms present within the last month on a 3-point scale and the associated impact of the symptom manifestations on them (i.e. Caregiver Distress) using a 5-point scale. The NPI-Q provides symptom Severity and Distress ratings for each symptom reported, and total Severity and Distress scores reflecting the sum of individual domain scores. NPI-Q Severity score range: 0-36 (lower is better).
Measured: Baseline, 1 year
Number of Patients With Seizures
Number of participants that reported seizures during follow up time
Measured: Baseline, 1 year
Number of Discontinuations From Montelukast
Number of participants that stopped taking Montelukast during follow up time
Measured: Baseline, 1 year
Secondary outcomes (4)
CSF Amyloid
A lumbar puncture will be done at baseline and at 12 months follow up Approximately 30-45 ml of CSF will be collected using sterile polypropylene collection tubes.
Amyloid-β42 is reported as pg/ml.
Measured: Baseline, 1 year
CSF Tau Levels
CSF tau protein (CSF-tau) is found in most patients with Alzheimer's disease. A lumbar puncture will be done at baseline and at 12 months follow up. Approximately 30-45 ml of CSF will be collected using sterile polypropylene collection tubes. Results will be reported as Phospho tau (p-tau181) in pg/ml.
Measured: Baseline, 1 year
Clinical Dementia Rating (CDR) Score
The CDR rates each of the six general domains (or boxes) involving memory, orientation, judgment and problem-solving, community affairs, home and hobbies, and personal care, and a global rating is then generated, ranging from 0 to 3. A score of 0 = normal, 0.5 = very mild dementia, 1 = mild dementia, 2 = moderate dementia, and 3 = severe dementia.
Measured: Baseline, 1 year
NIH Toolbox Cognition Battery (NIHTB-CB)
The NIH Toolbox® is a computer-based comprehensive set of neuro-behavioral measurements that reliably and validly assesses neurocognitive sub-domains in clinical trials, including working memory, episodic memory, processing speed, language, attention and executive function. The fluid cognitive composite (FCC) score is derived by averaging the standard scores of each of the fluid tests (Picture Sequence Memory, List Sorting, Pattern Comparison, Flanker, and Dimensional Change Card Sort.), and then deriving standard scores based on this new distribution. The fully-adjusted FCC T-score is reported. Higher score indicates with better performance. The score ranged from a minimum of 19 (0th percentile) to a maximum of 58 (79th percentile) in this sample. The population-level T-score and percentile rank range from 23 (0.3th percentile) to 77 (99.6th percentile) with mean=50 and SD=10.
Measured: Baseline, 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jun 2019
- Study start25 Sep 2019
- Primary completion18 Nov 2022
- Study completion18 Nov 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ihab Hajjar, Emory University
- Investigators
- Ihab Hajjar, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03991988
- Sponsor's protocol ID
- IRB00111553
- Status last verified
- Feb 2024
- First submitted
- 18 Jun 2019
- Last updated
- 7 Mar 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Montelukast Therapy on Alzheimer's Disease (EMERALD)
- ClinicalTrials.gov ID
- NCT03991988
- Acronym / sponsor ID
- IRB00111553
- Conditions
- Alzheimer Disease
- Keywords
- Alzheimer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Study start
- 25 Sep 2019 (actual)
- Primary completion
- 18 Nov 2022 (actual)
- Study completion
- 18 Nov 2022 (actual)
- First posted
- 19 Jun 2019 (actual)
- Results
- Posted 7 Mar 2024
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 one-year, double-blind placebo-controlled randomized clinical trial that compares montelukast to placebo in individuals with mild cognitive impairment (MCI) and early Alzheimer's disease (AD) dementia. The measures include cognitive function, cerebrospinal fluid (CSF) biomarkers and neuroimaging (cerebral perfusion and markers of vascular brain damage).
Participants will be treated with montelukast (escalating doses:10, 20 to 40 mg) or matched placebo.
Detailed description
Treatment options for Alzheimer's disease (AD) remain limited, especially treatments linking neurovascular and neuroinflammatory changes with clinical manifestations of the disease. Prior research studies have documented a positive effect of cysteinyl leukotriene type 1 (cysLT-1) receptor antagonist, particularly Montelukast, on inflammatory processes in the brain and on neuronal injury, blood-brain-barrier (BBB) integrity, and amyloid-β42 (Aβ) protein accumulation. Although montelukast is currently in use for the treatment of inflammatory diseases e.g. bronchial asthma and exercise-induced bronchospasm, its effects on memory and thinking abilities and on AD biomarkers are yet to be fully understood.
This is a single site randomized controlled trial at Emory University that compares the effects of montelukast vs. placebo on memory and thinking abilities, as well as on brain imaging and markers of brain degeneration. Each participant will undergo a screening process following informed consent to determine if they meet study eligibility criteria. Participants will be enrolled in the study for 1 year.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Montelukast Group | Experimental | Drug: MontelukastMontelukast (10, 20, or 40 mg) |
| Placebo Group | Placebo comparator | Drug: Placebo oral tabletMatched placebo pill |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Age: 50 years or older
- MCI group will be defined based on:
- Early AD dementia group will be defined based on:
- Abnormal memory function documented using the Logical Memory subscale (Delayed Paragraph Recall, Paragraph A only) from the Wechsler Memory Scale-Revised (the maximum score is 25): [<11 for 16 or more years of education; <9 for 8-15 years of education; <6 for <7 years of education];
- Montreal Cognitive Assessment (MoCA) <26;
Key exclusion criteria (15 listed)
- Intolerance to Montelukast;
- Current diagnosis of bronchial asthma or exercise-induced bronchospasm and currently on Montelukast or other leukotriene receptor antagonists (Zafirlukast, Pranlukast);
- Liver disease (elevated liver enzymes (>2x normal): Alanine aminotransferase (ALT), AST, alkaline phosphatase, total bilirubin);
- Renal disease (Creatinine >2.0 mg/dl), platelets<50,000/μl, or INR>1.9;
- Diagnosis of any neurological or psychiatric disorders that affects cognition such as uncontrolled depression, schizophrenia, Parkinson's disease or use of anti-Parkinsonian therapies (unless used for essential tremor), multiple sclerosis, or other active medical condition that in the judgment of the study physicians would affect the safety of the subject or scientific integrity of the study;
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 |
|---|---|---|
| MontelukastParticipants in this arm will take a pill of Montelukast daily on escalating doses: 10, 20 to 40 mg. All participants will be initiated on 10 mg. The dose will be increased in 2-week increments to 20 mg and 40 mg as long as participants report no intolerable symptoms or adverse events. | Drug | Montelukast Group |
| Placebo oral tabletParticipants in this arm will take a matched placebo pill daily | Drug | Placebo Group |
Primary outcome
Number of Participants With Any Gastrointestinal (GI) Symptoms
Time frame: Baseline, 1 year
Number of participants with any GI symptoms reported: diarrhea, nausea, vomiting
Number of Participants With Reported Anaphylaxis
Time frame: Baseline, 1 year
Number of participants with reported anaphylaxis during follow up time
Number of Participants With Elevated Liver Enzymes
Time frame: Baseline, 1 year
Number of participants with elevated liver enzymes during follow up
Prothrombin Time (PT)/ International Normalized Ratio (INR)
Time frame: Baseline, 1 year
Prothrombin time (PT)/ international normalized ratio (INR) will be measured at baseline and 1 year.
Neuropsychiatric Inventory Questionnaire (NPI-Q) Score
Time frame: Baseline, 1 year
The NPI-Q is designed to be a self-administered questionnaire completed by informants about patients for whom they care. Each of the 12 NPI-Q domains contains a survey question that reflects cardinal symptoms of that domain. Initial responses to each domain question are "Yes" (present) or "No" (absent). If the response to the domain question is "No", the informant goes to the next question. If "Yes", the informant then rates both the Severity of the symptoms present within the last month on a 3-point scale and the associated impact of the symptom manifestations on them (i.e. Caregiver Distress) using a 5-point scale. The NPI-Q provides symptom Severity and Distress ratings for each symptom reported, and total Severity and Distress scores reflecting the sum of individual domain scores. NPI-Q Severity score range: 0-36 (lower is better).
Number of Patients With Seizures
Time frame: Baseline, 1 year
Number of participants that reported seizures during follow up time
Number of Discontinuations From Montelukast
Time frame: Baseline, 1 year
Number of participants that stopped taking Montelukast during follow up time
4 secondary outcomes
CSF Amyloid
Time frame: Baseline, 1 year
CSF Tau Levels
Time frame: Baseline, 1 year
Clinical Dementia Rating (CDR) Score
Time frame: Baseline, 1 year
NIH Toolbox Cognition Battery (NIHTB-CB)
Time frame: Baseline, 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Ihab Hajjar principal investigator
Emory University
4 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 Montelukast in people with Alzheimer Disease, run by Emory University at 4 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 13 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: finished, as of the sponsor's last update on 7 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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?
Yes. Results are posted in the registry (first posted 7 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With Any Gastrointestinal (GI) Symptoms (time frame: Baseline, 1 year). The study lists 7 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 7 Mar 2024.