Trial Outcomes & Findings for Montelukast Therapy on Alzheimer's Disease (NCT NCT03991988)
NCT ID: NCT03991988
Last Updated: 2024-03-07
Results Overview
Number of participants with any GI symptoms reported: diarrhea, nausea, vomiting
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
32 participants
Primary outcome timeframe
Baseline, 1 year
Results posted on
2024-03-07
Participant Flow
Participant milestones
| Measure |
Montelukast Group
Montelukast (10, 20, or 40 mg)
Montelukast: 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 Group
Matched placebo pill
Placebo oral tablet: Participants in this arm will take a matched placebo pill daily
|
|---|---|---|
|
Overall Study
STARTED
|
16
|
16
|
|
Overall Study
COMPLETED
|
14
|
14
|
|
Overall Study
NOT COMPLETED
|
2
|
2
|
Reasons for withdrawal
| Measure |
Montelukast Group
Montelukast (10, 20, or 40 mg)
Montelukast: 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 Group
Matched placebo pill
Placebo oral tablet: Participants in this arm will take a matched placebo pill daily
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
2
|
2
|
Baseline Characteristics
Montelukast Therapy on Alzheimer's Disease
Baseline characteristics by cohort
| Measure |
Montelukast Group
n=16 Participants
Montelukast (10, 20, or 40 mg)
Montelukast: 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 Group
n=16 Participants
Matched placebo pill
Placebo oral tablet: Participants in this arm will take a matched placebo pill daily
|
Total
n=32 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
71.3 years
STANDARD_DEVIATION 8.8 • n=5 Participants
|
73.9 years
STANDARD_DEVIATION 7.7 • n=7 Participants
|
72.6 years
STANDARD_DEVIATION 8.2 • n=5 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
16 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
32 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
4 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
12 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
16 participants
n=5 Participants
|
16 participants
n=7 Participants
|
32 participants
n=5 Participants
|
|
Mild Cognitive Impairment (MCI)
|
10 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
|
Dementia
|
6 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, 1 yearNumber of participants with any GI symptoms reported: diarrhea, nausea, vomiting
Outcome measures
| Measure |
Montelukast Group
n=16 Participants
Montelukast (10, 20, or 40 mg)
Montelukast: 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 Group
n=16 Participants
Matched placebo pill
Placebo oral tablet: Participants in this arm will take a matched placebo pill daily
|
|---|---|---|
|
Number of Participants With Any Gastrointestinal (GI) Symptoms
|
1 Participants
|
1 Participants
|
PRIMARY outcome
Timeframe: Baseline, 1 yearNumber of participants with reported anaphylaxis during follow up time
Outcome measures
| Measure |
Montelukast Group
n=16 Participants
Montelukast (10, 20, or 40 mg)
Montelukast: 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 Group
n=16 Participants
Matched placebo pill
Placebo oral tablet: Participants in this arm will take a matched placebo pill daily
|
|---|---|---|
|
Number of Participants With Reported Anaphylaxis
|
1 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Baseline, 1 yearNumber of participants with elevated liver enzymes during follow up
Outcome measures
| Measure |
Montelukast Group
n=16 Participants
Montelukast (10, 20, or 40 mg)
Montelukast: 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 Group
n=16 Participants
Matched placebo pill
Placebo oral tablet: Participants in this arm will take a matched placebo pill daily
|
|---|---|---|
|
Number of Participants With Elevated Liver Enzymes
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Baseline, 1 yearPopulation: Data captured from participants with CSF data or who completed a lumbar puncture procedure and have available results for PT/INR.
Prothrombin time (PT)/ international normalized ratio (INR) will be measured at baseline and 1 year.
Outcome measures
| Measure |
Montelukast Group
n=11 Participants
Montelukast (10, 20, or 40 mg)
Montelukast: 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 Group
n=12 Participants
Matched placebo pill
Placebo oral tablet: Participants in this arm will take a matched placebo pill daily
|
|---|---|---|
|
Prothrombin Time (PT)/ International Normalized Ratio (INR)
Baseline
|
1.05 ratio
Standard Error 0.02
|
1.02 ratio
Standard Error 0.01
|
|
Prothrombin Time (PT)/ International Normalized Ratio (INR)
1 year
|
—
|
1.05 ratio
Standard Error 0.05
|
PRIMARY outcome
Timeframe: Baseline, 1 yearThe 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).
Outcome measures
| Measure |
Montelukast Group
n=16 Participants
Montelukast (10, 20, or 40 mg)
Montelukast: 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 Group
n=16 Participants
Matched placebo pill
Placebo oral tablet: Participants in this arm will take a matched placebo pill daily
|
|---|---|---|
|
Neuropsychiatric Inventory Questionnaire (NPI-Q) Score
Baseline
|
5.00 score on a scale
Standard Error 0.97
|
2.62 score on a scale
Standard Error 0.95
|
|
Neuropsychiatric Inventory Questionnaire (NPI-Q) Score
1 year
|
5.68 score on a scale
Standard Error 1.04
|
2.73 score on a scale
Standard Error 1.02
|
PRIMARY outcome
Timeframe: Baseline, 1 yearNumber of participants that reported seizures during follow up time
Outcome measures
| Measure |
Montelukast Group
n=16 Participants
Montelukast (10, 20, or 40 mg)
Montelukast: 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 Group
n=16 Participants
Matched placebo pill
Placebo oral tablet: Participants in this arm will take a matched placebo pill daily
|
|---|---|---|
|
Number of Patients With Seizures
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Baseline, 1 yearPopulation: This outcome measured the number of participants that stopped taking Montelukast. This outcome was not assessed in the Placebo group.
Number of participants that stopped taking Montelukast during follow up time
Outcome measures
| Measure |
Montelukast Group
n=16 Participants
Montelukast (10, 20, or 40 mg)
Montelukast: 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 Group
Matched placebo pill
Placebo oral tablet: Participants in this arm will take a matched placebo pill daily
|
|---|---|---|
|
Number of Discontinuations From Montelukast
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline, 1 yearPopulation: 22 participants with CSF amyloid data captured (11 in Montelukast group and 11 in placebo group).
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.
Outcome measures
| Measure |
Montelukast Group
n=11 Participants
Montelukast (10, 20, or 40 mg)
Montelukast: 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 Group
n=11 Participants
Matched placebo pill
Placebo oral tablet: Participants in this arm will take a matched placebo pill daily
|
|---|---|---|
|
CSF Amyloid
Baseline
|
849.4 pg/ml
Standard Error 77.34
|
704.6 pg/ml
Standard Error 89.48
|
|
CSF Amyloid
1 year
|
795.5 pg/ml
Standard Error 76.60
|
695.2 pg/ml
Standard Error 88.11
|
SECONDARY outcome
Timeframe: Baseline, 1 yearPopulation: 22 participants with CSF tau data captured (11 in Montelukast group and 11 in placebo group).
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.
Outcome measures
| Measure |
Montelukast Group
n=11 Participants
Montelukast (10, 20, or 40 mg)
Montelukast: 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 Group
n=11 Participants
Matched placebo pill
Placebo oral tablet: Participants in this arm will take a matched placebo pill daily
|
|---|---|---|
|
CSF Tau Levels
Baseline
|
20.6 pg/ml
Standard Error 2.42
|
22.8 pg/ml
Standard Error 2.81
|
|
CSF Tau Levels
1 year
|
21.1 pg/ml
Standard Error 2.48
|
21.9 pg/ml
Standard Error 2.86
|
SECONDARY outcome
Timeframe: Baseline, 1 yearThe 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.
Outcome measures
| Measure |
Montelukast Group
n=16 Participants
Montelukast (10, 20, or 40 mg)
Montelukast: 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 Group
n=16 Participants
Matched placebo pill
Placebo oral tablet: Participants in this arm will take a matched placebo pill daily
|
|---|---|---|
|
Clinical Dementia Rating (CDR) Score
Baseline
|
0.6 score on a scale
Standard Error 0.05
|
0.6 score on a scale
Standard Error 0.04
|
|
Clinical Dementia Rating (CDR) Score
1 year
|
0.7 score on a scale
Standard Error 0.07
|
0.7 score on a scale
Standard Error 0.07
|
SECONDARY outcome
Timeframe: Baseline, 1 yearThe 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.
Outcome measures
| Measure |
Montelukast Group
n=16 Participants
Montelukast (10, 20, or 40 mg)
Montelukast: 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 Group
n=16 Participants
Matched placebo pill
Placebo oral tablet: Participants in this arm will take a matched placebo pill daily
|
|---|---|---|
|
NIH Toolbox Cognition Battery (NIHTB-CB)
Baseline
|
35.2 t-score
Standard Error 2.53
|
35.4 t-score
Standard Error 2.93
|
|
NIH Toolbox Cognition Battery (NIHTB-CB)
1 year
|
33.9 t-score
Standard Error 2.89
|
37.3 t-score
Standard Error 3.41
|
Adverse Events
Montelukast Group
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Placebo Group
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Montelukast Group
n=16 participants at risk
Montelukast (10, 20, or 40 mg)
Montelukast: Participants in this arm will take a pill of Montelukast daily on escalating doses: 10, 20 to 40 mg.
All participants were initiated on 10 mg, and the dose increased in 2-week increments to 20 mg and 40 mg as long as participants report no intolerable symptoms or adverse events.
|
Placebo Group
n=16 participants at risk
Matched placebo pill
Placebo oral tablet: Participants in this arm will take a matched placebo pill daily
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
6.2%
1/16 • Number of events 1 • During follow up time, an average of 1 year
All participants on the Montelukast arm with reported AEs were safely escalated to 40 mg dose, and all their AEs resolved spontaneously with no sequelae. AE results were collected altogether (not dose based).
|
0.00%
0/16 • During follow up time, an average of 1 year
All participants on the Montelukast arm with reported AEs were safely escalated to 40 mg dose, and all their AEs resolved spontaneously with no sequelae. AE results were collected altogether (not dose based).
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/16 • During follow up time, an average of 1 year
All participants on the Montelukast arm with reported AEs were safely escalated to 40 mg dose, and all their AEs resolved spontaneously with no sequelae. AE results were collected altogether (not dose based).
|
6.2%
1/16 • Number of events 1 • During follow up time, an average of 1 year
All participants on the Montelukast arm with reported AEs were safely escalated to 40 mg dose, and all their AEs resolved spontaneously with no sequelae. AE results were collected altogether (not dose based).
|
|
General disorders
Rash
|
6.2%
1/16 • Number of events 1 • During follow up time, an average of 1 year
All participants on the Montelukast arm with reported AEs were safely escalated to 40 mg dose, and all their AEs resolved spontaneously with no sequelae. AE results were collected altogether (not dose based).
|
0.00%
0/16 • During follow up time, an average of 1 year
All participants on the Montelukast arm with reported AEs were safely escalated to 40 mg dose, and all their AEs resolved spontaneously with no sequelae. AE results were collected altogether (not dose based).
|
|
General disorders
Dizziness
|
6.2%
1/16 • Number of events 1 • During follow up time, an average of 1 year
All participants on the Montelukast arm with reported AEs were safely escalated to 40 mg dose, and all their AEs resolved spontaneously with no sequelae. AE results were collected altogether (not dose based).
|
0.00%
0/16 • During follow up time, an average of 1 year
All participants on the Montelukast arm with reported AEs were safely escalated to 40 mg dose, and all their AEs resolved spontaneously with no sequelae. AE results were collected altogether (not dose based).
|
|
General disorders
Headache
|
0.00%
0/16 • During follow up time, an average of 1 year
All participants on the Montelukast arm with reported AEs were safely escalated to 40 mg dose, and all their AEs resolved spontaneously with no sequelae. AE results were collected altogether (not dose based).
|
6.2%
1/16 • Number of events 1 • During follow up time, an average of 1 year
All participants on the Montelukast arm with reported AEs were safely escalated to 40 mg dose, and all their AEs resolved spontaneously with no sequelae. AE results were collected altogether (not dose based).
|
|
General disorders
Fatigue
|
0.00%
0/16 • During follow up time, an average of 1 year
All participants on the Montelukast arm with reported AEs were safely escalated to 40 mg dose, and all their AEs resolved spontaneously with no sequelae. AE results were collected altogether (not dose based).
|
6.2%
1/16 • Number of events 1 • During follow up time, an average of 1 year
All participants on the Montelukast arm with reported AEs were safely escalated to 40 mg dose, and all their AEs resolved spontaneously with no sequelae. AE results were collected altogether (not dose based).
|
|
General disorders
Low Mood
|
0.00%
0/16 • During follow up time, an average of 1 year
All participants on the Montelukast arm with reported AEs were safely escalated to 40 mg dose, and all their AEs resolved spontaneously with no sequelae. AE results were collected altogether (not dose based).
|
6.2%
1/16 • Number of events 1 • During follow up time, an average of 1 year
All participants on the Montelukast arm with reported AEs were safely escalated to 40 mg dose, and all their AEs resolved spontaneously with no sequelae. AE results were collected altogether (not dose based).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place