Montelukast Therapy on Alzheimer's Disease

NCT03991988 | Completed Phase 2 Results FDA Drug

• 1 other identifier: IRB00111553
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 4

Brief 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. 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.

Conditions

Alzheimer Disease

Keywords

Alzheimer

Outcome Measures

Primary Outcomes (7)

• Number of Participants With Any Gastrointestinal (GI) Symptoms

  Number of participants with any GI symptoms reported: diarrhea, nausea, vomiting

  Baseline, 1 year

• Number of Participants With Reported Anaphylaxis

  Number of participants with reported anaphylaxis during follow up time

  Baseline, 1 year

• Number of Participants With Elevated Liver Enzymes

  Number of participants with elevated liver enzymes during follow up

  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.

  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).

  Baseline, 1 year

• Number of Patients With Seizures

  Number of participants that reported seizures during follow up time

  Baseline, 1 year

• Number of Discontinuations From Montelukast

  Number of participants that stopped taking Montelukast during follow up time

  Baseline, 1 year

Secondary Outcomes (4)

• CSF Amyloid

  Baseline, 1 year

• CSF Tau Levels

  Baseline, 1 year

• Clinical Dementia Rating (CDR) Score

  Baseline, 1 year

• NIH Toolbox Cognition Battery (NIHTB-CB)

  Baseline, 1 year

Study Arms (2)

Montelukast Group

EXPERIMENTAL

Montelukast (10, 20, or 40 mg)

Drug: Montelukast

Placebo Group

PLACEBO COMPARATOR

Matched placebo pill

Drug: Placebo oral tablet

Interventions

Montelukast DRUG

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.

Montelukast Group

Placebo oral tablet DRUG

Participants in this arm will take a matched placebo pill daily

Placebo Group

Eligibility Criteria

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

You may qualify if:

• Age: 50 years or older
• MCI group will be defined based on:
• (i) Subjective memory concern;
• (ii) 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): \[\<11 for 16 or more years of education; \<9 for 8-15 years of education; \<6 for \<7 years of education\];
• (iii) Montreal Cognitive Assessment (MoCA) \< 26;
• (iv) Clinical Dementia Rating (CDR) scale /Memory box score=0.5;
• (v) General functional performance sufficiently preserved (Functional Assessment Questionnaire ≤5).
• Early AD dementia group will be defined based on:
• (i) Subjective memory concern;
• (ii) 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): \[\<11 for 16 or more years of education; \<9 for 8-15 years of education; \<6 for \<7 years of education\];
• (iii) Montreal Cognitive Assessment (MoCA) \<26;
• (iv) Clinical Dementia Rating scale/Memory box score 1 or 2;
• (v) Early AD dementia defined as Functional Assessment Staging Test (FAST) of 4 or 5

You may not qualify if:

• 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);
• 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.

Sponsors & Collaborators

• Emory University: lead

Study Sites (4)

Emory Clinic

Atlanta, Georgia, 30322, United States

Location

Emory University Hospital Clinical Research Network

Atlanta, Georgia, 30322, United States

Location

Executive Park

Atlanta, Georgia, 30329, United States

Location

Wesley Woods

Atlanta, Georgia, 30329, United States

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

montelukast

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

A limitation of the study is its relatively small sample size.

Results Point of Contact

• Title: Dr. Ihab Hajjar
• Organization: Emory University

ihajjar@emory.edu

4047121763

Study Officials

• Ihab Hajjar

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: June 18, 2019
• First Posted: June 19, 2019
• Study Start: September 25, 2019
• Primary Completion: November 18, 2022
• Study Completion: November 18, 2022
• Last Updated: March 7, 2024
• Results First Posted: March 7, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)