Trial Outcomes & Findings for Effect of Galantamine on Inflammation and Cognition (NCT NCT03384784)
NCT ID: NCT03384784
Last Updated: 2024-10-17
Results Overview
Cognitive function will be assessed 4 times at Lab Visits. Executive function was measured by the task switch cost from the Color shape task, measured in ms. Executive function was also measured via response time (ms) and accuracy (# correct) on an N-back working memory task. Verbal learning and memory were measured by the Total Recall and Delayed Recall, respectively, from the Hopkins Verbal Learning Test. Response inhibition was measured by the stop signal reaction time (ms) from the Stop Signal Task. A composite score will be created by computed standardized z-scores for each measure (where the mean is 0 and the standard deviation is 1) and then averaging the z-scores. Measures of response time were reverse coded such that higher z-scores indicate better cognitive performance. The primary outcome is the change from baseline cognitive function after 12 weeks of treatment. Change in cognition will be measured during each treatment arm.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
63 participants
Primary outcome timeframe
Period1 Lab 1 (Week 0), Period 1 Lab 2 (Week 12), Period 2 Lab 1 (Week 16), Period 2 Lab 2 (Week 28)
Results posted on
2024-10-17
Participant Flow
Because there was a gap between enrollment and assignment to group, some participants were lost to follow-up between those time points.
Participant milestones
| Measure |
Galantamine First
This is a crossover study such that all participants receive both placebo and galantamine. Participants were randomized to receive galantamine first and placebo second. Timepoints Week 0 through Week 12 represent the first period and Weeks 16 through 28 represent the second period.
This study follows the FDA-recommended dosing regimen for galantamine extended release (GAL ER): 4 weeks at 8 mg (once a day), 4 weeks at 16 mg (once a day), and 4 weeks at 24 mg (once a day).
The University of Pennsylvania Investigational Drug Service (IDS) will oversee the randomization of all study medication, purchase study medication, manufacture matched placebo, encapsulate and package them in blister packs to maintain double-blind procedures.
Galantamine: The study will be performed using the 8mg, 16mg and 24mg doses of galantamine hydrobromide-ER. The dosing regimen will be an initial 4 weeks of drug run-up at the lowest 8mg q.d. dose, followed by 16mg q.d. for the following 4 weeks, and the dose will be increased for the last 4 weeks to 24mg. Participants will be instructed to take one 8mg 16mg or 24mg pill (galantamine-ER or placebo) every morning, preferably with food.
|
Placebo First
This is a crossover study such that all participants receive both placebo and galantamine. Participants were randomized to receive placebo first and galantamine second. Timepoints Week 0 through Week 12 represent the first period and Weeks 16 through 28 represent the second period.
Placebo ingredients will be purchased, encapsulated, and packaged into blister packs by the IDS at the University of Pennsylvania. Both active medication and placebo will look identical.
The study medication assignments for each participant in this project is randomized and counterbalanced. This means that approximately 50% of participants will take galantamine during the first medication period, followed by the placebo in the second medication period. Alternatively, approximately 50% of participants will take the placebo during the first medication period, followed by galantamine during the second medication period.
Placebo: Matched placebo will be made in-house using lactulose filler in gel capsules. Participants will be instructed to take one pills every morning for 12 weeks.
|
|---|---|---|
|
First Intervention (12 Weeks)
STARTED
|
28
|
30
|
|
First Intervention (12 Weeks)
COMPLETED
|
25
|
25
|
|
First Intervention (12 Weeks)
NOT COMPLETED
|
3
|
5
|
|
Washout (4 Weeks)
STARTED
|
25
|
25
|
|
Washout (4 Weeks)
COMPLETED
|
17
|
24
|
|
Washout (4 Weeks)
NOT COMPLETED
|
8
|
1
|
|
Second Intervention (12 Weeks)
STARTED
|
17
|
24
|
|
Second Intervention (12 Weeks)
COMPLETED
|
16
|
21
|
|
Second Intervention (12 Weeks)
NOT COMPLETED
|
1
|
3
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Effect of Galantamine on Inflammation and Cognition
Baseline characteristics by cohort
| Measure |
Galantamine First
n=28 Participants
This is a crossover study such that all participants receive both placebo and galantamine. Participants were randomized to receive galantamine first and placebo second. Timepoints Week 0 through Week 12 represent the first period and Weeks 16 through 28 represent the second period.
This study follows the FDA-recommended dosing regimen for galantamine extended release (GAL ER): 4 weeks at 8 mg (once a day), 4 weeks at 16 mg (once a day), and 4 weeks at 24 mg (once a day).
The University of Pennsylvania Investigational Drug Service (IDS) will oversee the randomization of all study medication, purchase study medication, manufacture matched placebo, encapsulate and package them in blister packs to maintain double-blind procedures.
Galantamine: The study will be performed using the 8mg, 16mg and 24mg doses of galantamine hydrobromide-ER. The dosing regimen will be an initial 4 weeks of drug run-up at the lowest 8mg q.d. dose, followed by 16mg q.d. for the following 4 weeks, and the dose will be increased for the last 4 weeks to 24mg. Participants will be instructed to take one 8mg 16mg or 24mg pill (galantamine-ER or placebo) every morning, preferably with food.
|
Placebo First
n=30 Participants
This is a crossover study such that all participants receive both placebo and galantamine. Participants were randomized to receive galantamine first and placebo second. Timepoints Week 0 through Week 12 represent the first period and Weeks 16 through 28 represent the second period.
Placebo ingredients will be purchased, encapsulated, and packaged into blister packs by the IDS at the University of Pennsylvania. Both active medication and placebo will look identical.
The study medication assignments for each participant in this project is randomized and counterbalanced. This means that approximately 50% of participants will take galantamine during the first medication period, followed by the placebo in the second medication period. Alternatively, approximately 50% of participants will take the placebo during the first medication period, followed by galantamine during the second medication period.
Placebo: Matched placebo will be made in-house using lactulose filler in gel capsules. Participants will be instructed to take one pills every morning for 12 weeks.
|
Total
n=58 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
28 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
58 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
57.9 years
STANDARD_DEVIATION 3.7 • n=5 Participants
|
57.3 years
STANDARD_DEVIATION 5.1 • n=7 Participants
|
57.6 years
STANDARD_DEVIATION 4.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
23 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
45 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
25 Participants
n=5 Participants
|
29 Participants
n=7 Participants
|
54 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
|
21 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
40 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
28 participants
n=5 Participants
|
30 participants
n=7 Participants
|
58 participants
n=5 Participants
|
|
Smoking History
Non-Smoker
|
10 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
32 Participants
n=5 Participants
|
|
Smoking History
Current Smoker
|
18 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
|
CD4 Levels at Intake
|
769.8 cells/microliter
STANDARD_DEVIATION 311.2 • n=5 Participants
|
611.6 cells/microliter
STANDARD_DEVIATION 201.1 • n=7 Participants
|
687.9 cells/microliter
STANDARD_DEVIATION 269.7 • n=5 Participants
|
|
Viral Load at Intake
Viral load < 50 copies/mL
|
25 Participants
n=5 Participants
|
28 Participants
n=7 Participants
|
53 Participants
n=5 Participants
|
|
Viral Load at Intake
Viral load > = 50 copies/mL
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Period1 Lab 1 (Week 0), Period 1 Lab 2 (Week 12), Period 2 Lab 1 (Week 16), Period 2 Lab 2 (Week 28)Population: Number analyzed at each time point reflects participants who had complete data for all cognitive measures.
Cognitive function will be assessed 4 times at Lab Visits. Executive function was measured by the task switch cost from the Color shape task, measured in ms. Executive function was also measured via response time (ms) and accuracy (# correct) on an N-back working memory task. Verbal learning and memory were measured by the Total Recall and Delayed Recall, respectively, from the Hopkins Verbal Learning Test. Response inhibition was measured by the stop signal reaction time (ms) from the Stop Signal Task. A composite score will be created by computed standardized z-scores for each measure (where the mean is 0 and the standard deviation is 1) and then averaging the z-scores. Measures of response time were reverse coded such that higher z-scores indicate better cognitive performance. The primary outcome is the change from baseline cognitive function after 12 weeks of treatment. Change in cognition will be measured during each treatment arm.
Outcome measures
| Measure |
Galantamine First
n=28 Participants
This is a crossover study such that all participants receive both placebo and galantamine. Participants were randomized to receive galantamine first and placebo second. Timepoints Week 0 through Week 12 represent the first period and Weeks 16 through 28 represent the second period.
This study follows the FDA-recommended dosing regimen for galantamine extended release (GAL ER): 4 weeks at 8 mg (once a day), 4 weeks at 16 mg (once a day), and 4 weeks at 24 mg (once a day).
The University of Pennsylvania Investigational Drug Service (IDS) will oversee the randomization of all study medication, purchase study medication, manufacture matched placebo, encapsulate and package them in blister packs to maintain double-blind procedures.
Galantamine: The study will be performed using the 8mg, 16mg and 24mg doses of galantamine hydrobromide-ER. The dosing regimen will be an initial 4 weeks of drug run-up at the lowest 8mg q.d. dose, followed by 16mg q.d. for the following 4 weeks, and the dose will be increased for the last 4 weeks to 24mg. Participants will be instructed to take one 8mg 16mg or 24mg pill (galantamine-ER or placebo) every morning, preferably with food.
|
Placebo First
n=30 Participants
This is a crossover study such that all participants receive both placebo and galantamine. Participants were randomized to receive placebo first and galantamine second. Timepoints Week 0 through Week 12 represent the first period and Weeks 16 through 28 represent the second period.
Placebo ingredients will be purchased, encapsulated, and packaged into blister packs by the IDS at the University of Pennsylvania. Both active medication and placebo will look identical.
The study medication assignments for each participant in this project is randomized and counterbalanced. This means that approximately 50% of participants will take galantamine during the first medication period, followed by the placebo in the second medication period. Alternatively, approximately 50% of participants will take the placebo during the first medication period, followed by galantamine during the second medication period.
Placebo: Matched placebo will be made in-house using lactulose filler in gel capsules. Participants will be instructed to take one pills every morning for 12 weeks.
|
|---|---|---|
|
Change in Cognition
Period 1 Lab 2 (Week 12)
|
0.068 Z-score
Standard Deviation 0.695
|
0.201 Z-score
Standard Deviation 0.615
|
|
Change in Cognition
Period1 Lab 1 (Week 0)
|
.018 Z-score
Standard Deviation .469
|
.12 Z-score
Standard Deviation .509
|
|
Change in Cognition
Period 2 Lab 1 (Week 16)
|
0.020 Z-score
Standard Deviation 0.746
|
0.440 Z-score
Standard Deviation 0.578
|
|
Change in Cognition
Period 2 Lab 2 (Week 28)
|
0.219 Z-score
Standard Deviation 0.806
|
0.490 Z-score
Standard Deviation 0.472
|
PRIMARY outcome
Timeframe: Period1 Lab 1 (Week 0), Period 1 Lab 2 (Week 12), Period 2 Lab 1 (Week 16), Period 2 Lab 2 (Week 28)Population: Number analyzed reflects participants who had complete data at each time point.
Cellular markers of immune activation will be measured in whole blood and soluble markers of immune activation will be measured in plasma at Lab Visits. The primary outcome is the change in monocyte and T cell surface activation and soluble markers after 12 weeks of treatment. Because this is a within-subject crossover study, changes in cellular markers will be measured during each treatment arm.
Outcome measures
| Measure |
Galantamine First
n=28 Participants
This is a crossover study such that all participants receive both placebo and galantamine. Participants were randomized to receive galantamine first and placebo second. Timepoints Week 0 through Week 12 represent the first period and Weeks 16 through 28 represent the second period.
This study follows the FDA-recommended dosing regimen for galantamine extended release (GAL ER): 4 weeks at 8 mg (once a day), 4 weeks at 16 mg (once a day), and 4 weeks at 24 mg (once a day).
The University of Pennsylvania Investigational Drug Service (IDS) will oversee the randomization of all study medication, purchase study medication, manufacture matched placebo, encapsulate and package them in blister packs to maintain double-blind procedures.
Galantamine: The study will be performed using the 8mg, 16mg and 24mg doses of galantamine hydrobromide-ER. The dosing regimen will be an initial 4 weeks of drug run-up at the lowest 8mg q.d. dose, followed by 16mg q.d. for the following 4 weeks, and the dose will be increased for the last 4 weeks to 24mg. Participants will be instructed to take one 8mg 16mg or 24mg pill (galantamine-ER or placebo) every morning, preferably with food.
|
Placebo First
n=30 Participants
This is a crossover study such that all participants receive both placebo and galantamine. Participants were randomized to receive placebo first and galantamine second. Timepoints Week 0 through Week 12 represent the first period and Weeks 16 through 28 represent the second period.
Placebo ingredients will be purchased, encapsulated, and packaged into blister packs by the IDS at the University of Pennsylvania. Both active medication and placebo will look identical.
The study medication assignments for each participant in this project is randomized and counterbalanced. This means that approximately 50% of participants will take galantamine during the first medication period, followed by the placebo in the second medication period. Alternatively, approximately 50% of participants will take the placebo during the first medication period, followed by galantamine during the second medication period.
Placebo: Matched placebo will be made in-house using lactulose filler in gel capsules. Participants will be instructed to take one pills every morning for 12 weeks.
|
|---|---|---|
|
Change in Inflammation (MCP-1)
Period1 Lab 1 (Week 0)
|
405.00 pg/mL
Standard Deviation 277.68
|
402.05 pg/mL
Standard Deviation 206.56
|
|
Change in Inflammation (MCP-1)
Period1 Lab 2 (Week 12)
|
423.33 pg/mL
Standard Deviation 266.71
|
337.01 pg/mL
Standard Deviation 163.38
|
|
Change in Inflammation (MCP-1)
Period2 Lab 1 (Week 16)
|
411.71 pg/mL
Standard Deviation 221.34
|
350.00 pg/mL
Standard Deviation 149.55
|
|
Change in Inflammation (MCP-1)
Period2 Lab 2 (Week 28)
|
410.76 pg/mL
Standard Deviation 300.29
|
334.91 pg/mL
Standard Deviation 155.85
|
PRIMARY outcome
Timeframe: Period1 Lab 1 (Week 0), Period 1 Lab 2 (Week 12), Period 2 Lab 1 (Week 16), Period 2 Lab 2 (Week 28)Population: Number analyzed reflects participants with complete data for this measure at each time point.
Cellular markers of immune activation will be measured in whole blood and soluble markers of immune activation will be measured in plasma at Lab Visits. The primary outcome is the change in monocyte and T cell surface activation and soluble markers after 12 weeks of treatment. Because this is a within-subject crossover study, changes in cellular markers will be measured during each treatment arm.
Outcome measures
| Measure |
Galantamine First
n=28 Participants
This is a crossover study such that all participants receive both placebo and galantamine. Participants were randomized to receive galantamine first and placebo second. Timepoints Week 0 through Week 12 represent the first period and Weeks 16 through 28 represent the second period.
This study follows the FDA-recommended dosing regimen for galantamine extended release (GAL ER): 4 weeks at 8 mg (once a day), 4 weeks at 16 mg (once a day), and 4 weeks at 24 mg (once a day).
The University of Pennsylvania Investigational Drug Service (IDS) will oversee the randomization of all study medication, purchase study medication, manufacture matched placebo, encapsulate and package them in blister packs to maintain double-blind procedures.
Galantamine: The study will be performed using the 8mg, 16mg and 24mg doses of galantamine hydrobromide-ER. The dosing regimen will be an initial 4 weeks of drug run-up at the lowest 8mg q.d. dose, followed by 16mg q.d. for the following 4 weeks, and the dose will be increased for the last 4 weeks to 24mg. Participants will be instructed to take one 8mg 16mg or 24mg pill (galantamine-ER or placebo) every morning, preferably with food.
|
Placebo First
n=30 Participants
This is a crossover study such that all participants receive both placebo and galantamine. Participants were randomized to receive placebo first and galantamine second. Timepoints Week 0 through Week 12 represent the first period and Weeks 16 through 28 represent the second period.
Placebo ingredients will be purchased, encapsulated, and packaged into blister packs by the IDS at the University of Pennsylvania. Both active medication and placebo will look identical.
The study medication assignments for each participant in this project is randomized and counterbalanced. This means that approximately 50% of participants will take galantamine during the first medication period, followed by the placebo in the second medication period. Alternatively, approximately 50% of participants will take the placebo during the first medication period, followed by galantamine during the second medication period.
Placebo: Matched placebo will be made in-house using lactulose filler in gel capsules. Participants will be instructed to take one pills every morning for 12 weeks.
|
|---|---|---|
|
Change in Inflammation (Percentage of CD14+ Monocytes Expressing CD8)
Period1 Lab 1 (Week 0)
|
7.125 percentage of monocytes expressing CD8
Standard Deviation 6.859
|
5.590 percentage of monocytes expressing CD8
Standard Deviation 4.528
|
|
Change in Inflammation (Percentage of CD14+ Monocytes Expressing CD8)
Period 1 Lab 2 (Week 12)
|
5.747 percentage of monocytes expressing CD8
Standard Deviation 5.789
|
5.221 percentage of monocytes expressing CD8
Standard Deviation 3.069
|
|
Change in Inflammation (Percentage of CD14+ Monocytes Expressing CD8)
Period 2 Lab 1 (Week 16)
|
4.329 percentage of monocytes expressing CD8
Standard Deviation 2.933
|
6.570 percentage of monocytes expressing CD8
Standard Deviation 6.738
|
|
Change in Inflammation (Percentage of CD14+ Monocytes Expressing CD8)
Period 2 Lab 2 (Week 28)
|
6.150 percentage of monocytes expressing CD8
Standard Deviation 5.257
|
6.916 percentage of monocytes expressing CD8
Standard Deviation 4.658
|
PRIMARY outcome
Timeframe: Period1 Lab 1 (Week 0), Period 1 Lab 2 (Week 12), Period 2 Lab 1 (Week 16), Period 2 Lab 2 (Week 28)Population: Number analyzed reflects participants with complete data for this measure at each time point.
Cellular markers of immune activation will be measured in whole blood and soluble markers of immune activation will be measured in plasma at Lab Visits. The primary outcome is the change in monocyte and T cell surface activation and soluble markers after 12 weeks of treatment. Because this is a within-subject crossover study, changes in cellular markers will be measured during each treatment arm.
Outcome measures
| Measure |
Galantamine First
n=28 Participants
This is a crossover study such that all participants receive both placebo and galantamine. Participants were randomized to receive galantamine first and placebo second. Timepoints Week 0 through Week 12 represent the first period and Weeks 16 through 28 represent the second period.
This study follows the FDA-recommended dosing regimen for galantamine extended release (GAL ER): 4 weeks at 8 mg (once a day), 4 weeks at 16 mg (once a day), and 4 weeks at 24 mg (once a day).
The University of Pennsylvania Investigational Drug Service (IDS) will oversee the randomization of all study medication, purchase study medication, manufacture matched placebo, encapsulate and package them in blister packs to maintain double-blind procedures.
Galantamine: The study will be performed using the 8mg, 16mg and 24mg doses of galantamine hydrobromide-ER. The dosing regimen will be an initial 4 weeks of drug run-up at the lowest 8mg q.d. dose, followed by 16mg q.d. for the following 4 weeks, and the dose will be increased for the last 4 weeks to 24mg. Participants will be instructed to take one 8mg 16mg or 24mg pill (galantamine-ER or placebo) every morning, preferably with food.
|
Placebo First
n=30 Participants
This is a crossover study such that all participants receive both placebo and galantamine. Participants were randomized to receive placebo first and galantamine second. Timepoints Week 0 through Week 12 represent the first period and Weeks 16 through 28 represent the second period.
Placebo ingredients will be purchased, encapsulated, and packaged into blister packs by the IDS at the University of Pennsylvania. Both active medication and placebo will look identical.
The study medication assignments for each participant in this project is randomized and counterbalanced. This means that approximately 50% of participants will take galantamine during the first medication period, followed by the placebo in the second medication period. Alternatively, approximately 50% of participants will take the placebo during the first medication period, followed by galantamine during the second medication period.
Placebo: Matched placebo will be made in-house using lactulose filler in gel capsules. Participants will be instructed to take one pills every morning for 12 weeks.
|
|---|---|---|
|
Change in Inflammation (CD14)
Period1 Lab 1 (Week 0)
|
1672.64 ng/ml
Standard Deviation 440.69
|
1645.42 ng/ml
Standard Deviation 741.79
|
|
Change in Inflammation (CD14)
Period 1 Lab 2 (Week 12)
|
1807.66 ng/ml
Standard Deviation 461.12
|
1512.70 ng/ml
Standard Deviation 498.86
|
|
Change in Inflammation (CD14)
Period 2 Lab 1 (Week 16)
|
1809.55 ng/ml
Standard Deviation 330.04
|
1517.90 ng/ml
Standard Deviation 515.77
|
|
Change in Inflammation (CD14)
Period 2 Lab 2 (Week 28)
|
1631.96 ng/ml
Standard Deviation 352.70
|
1521.68 ng/ml
Standard Deviation 480.99
|
PRIMARY outcome
Timeframe: Period1 Lab 1 (Week 0), Period 1 Lab 2 (Week 12), Period 2 Lab 1 (Week 16), Period 2 Lab 2 (Week 28)Population: Number analyzed reflects participants with complete data for this measure at each time point.
Cellular markers of immune activation will be measured in whole blood and soluble markers of immune activation will be measured in plasma at Lab Visits. The primary outcome is the change in monocyte and T cell surface activation and soluble markers after 12 weeks of treatment. Because this is a within-subject crossover study, changes in cellular markers will be measured during each treatment arm.
Outcome measures
| Measure |
Galantamine First
n=28 Participants
This is a crossover study such that all participants receive both placebo and galantamine. Participants were randomized to receive galantamine first and placebo second. Timepoints Week 0 through Week 12 represent the first period and Weeks 16 through 28 represent the second period.
This study follows the FDA-recommended dosing regimen for galantamine extended release (GAL ER): 4 weeks at 8 mg (once a day), 4 weeks at 16 mg (once a day), and 4 weeks at 24 mg (once a day).
The University of Pennsylvania Investigational Drug Service (IDS) will oversee the randomization of all study medication, purchase study medication, manufacture matched placebo, encapsulate and package them in blister packs to maintain double-blind procedures.
Galantamine: The study will be performed using the 8mg, 16mg and 24mg doses of galantamine hydrobromide-ER. The dosing regimen will be an initial 4 weeks of drug run-up at the lowest 8mg q.d. dose, followed by 16mg q.d. for the following 4 weeks, and the dose will be increased for the last 4 weeks to 24mg. Participants will be instructed to take one 8mg 16mg or 24mg pill (galantamine-ER or placebo) every morning, preferably with food.
|
Placebo First
n=30 Participants
This is a crossover study such that all participants receive both placebo and galantamine. Participants were randomized to receive placebo first and galantamine second. Timepoints Week 0 through Week 12 represent the first period and Weeks 16 through 28 represent the second period.
Placebo ingredients will be purchased, encapsulated, and packaged into blister packs by the IDS at the University of Pennsylvania. Both active medication and placebo will look identical.
The study medication assignments for each participant in this project is randomized and counterbalanced. This means that approximately 50% of participants will take galantamine during the first medication period, followed by the placebo in the second medication period. Alternatively, approximately 50% of participants will take the placebo during the first medication period, followed by galantamine during the second medication period.
Placebo: Matched placebo will be made in-house using lactulose filler in gel capsules. Participants will be instructed to take one pills every morning for 12 weeks.
|
|---|---|---|
|
Change in Inflammation (Percentage of CD14+ Monocytes Expressing CD163)
Period1 Lab 1 (Week 0)
|
88.68 percentage of monocytes expressing CD163
Standard Deviation 5.48
|
89.11 percentage of monocytes expressing CD163
Standard Deviation 6.99
|
|
Change in Inflammation (Percentage of CD14+ Monocytes Expressing CD163)
Period 1 Lab 2 (Week 12)
|
80.03 percentage of monocytes expressing CD163
Standard Deviation 20.67
|
83.90 percentage of monocytes expressing CD163
Standard Deviation 17.87
|
|
Change in Inflammation (Percentage of CD14+ Monocytes Expressing CD163)
Period 2 Lab 1 (Week 16)
|
86.64 percentage of monocytes expressing CD163
Standard Deviation 7.67
|
87.15 percentage of monocytes expressing CD163
Standard Deviation 8.95
|
|
Change in Inflammation (Percentage of CD14+ Monocytes Expressing CD163)
Period 2 Lab 2 (Week 28)
|
86.44 percentage of monocytes expressing CD163
Standard Deviation 5.06
|
90.94 percentage of monocytes expressing CD163
Standard Deviation 5.24
|
PRIMARY outcome
Timeframe: Period1 Lab 1 (Week 0), Period 1 Lab 2 (Week 12), Period 2 Lab 1 (Week 16), Period 2 Lab 2 (Week 28)Population: Number analyzed reflects participants with complete data for this measure at each time point.
Cellular markers of immune activation will be measured in whole blood and soluble markers of immune activation will be measured in plasma at Lab Visits. The primary outcome is the change in monocyte and T cell surface activation and soluble markers after 12 weeks of treatment. Because this is a within-subject crossover study, changes in cellular markers will be measured during each treatment arm.
Outcome measures
| Measure |
Galantamine First
n=28 Participants
This is a crossover study such that all participants receive both placebo and galantamine. Participants were randomized to receive galantamine first and placebo second. Timepoints Week 0 through Week 12 represent the first period and Weeks 16 through 28 represent the second period.
This study follows the FDA-recommended dosing regimen for galantamine extended release (GAL ER): 4 weeks at 8 mg (once a day), 4 weeks at 16 mg (once a day), and 4 weeks at 24 mg (once a day).
The University of Pennsylvania Investigational Drug Service (IDS) will oversee the randomization of all study medication, purchase study medication, manufacture matched placebo, encapsulate and package them in blister packs to maintain double-blind procedures.
Galantamine: The study will be performed using the 8mg, 16mg and 24mg doses of galantamine hydrobromide-ER. The dosing regimen will be an initial 4 weeks of drug run-up at the lowest 8mg q.d. dose, followed by 16mg q.d. for the following 4 weeks, and the dose will be increased for the last 4 weeks to 24mg. Participants will be instructed to take one 8mg 16mg or 24mg pill (galantamine-ER or placebo) every morning, preferably with food.
|
Placebo First
n=30 Participants
This is a crossover study such that all participants receive both placebo and galantamine. Participants were randomized to receive placebo first and galantamine second. Timepoints Week 0 through Week 12 represent the first period and Weeks 16 through 28 represent the second period.
Placebo ingredients will be purchased, encapsulated, and packaged into blister packs by the IDS at the University of Pennsylvania. Both active medication and placebo will look identical.
The study medication assignments for each participant in this project is randomized and counterbalanced. This means that approximately 50% of participants will take galantamine during the first medication period, followed by the placebo in the second medication period. Alternatively, approximately 50% of participants will take the placebo during the first medication period, followed by galantamine during the second medication period.
Placebo: Matched placebo will be made in-house using lactulose filler in gel capsules. Participants will be instructed to take one pills every morning for 12 weeks.
|
|---|---|---|
|
Change in Inflammation (Percentage of CD14+ Monocytes Expressing CD16)
Period 2 Lab 1 (Week 16)
|
74.78 percentage of monocytes expressing CD16
Standard Deviation 15.27
|
69.04 percentage of monocytes expressing CD16
Standard Deviation 17.37
|
|
Change in Inflammation (Percentage of CD14+ Monocytes Expressing CD16)
Period1 Lab 1 (Week 0)
|
64.18 percentage of monocytes expressing CD16
Standard Deviation 19.49
|
64.90 percentage of monocytes expressing CD16
Standard Deviation 20.14
|
|
Change in Inflammation (Percentage of CD14+ Monocytes Expressing CD16)
Period 1 Lab 2 (Week 12)
|
67.44 percentage of monocytes expressing CD16
Standard Deviation 17.88
|
68.02 percentage of monocytes expressing CD16
Standard Deviation 17.79
|
|
Change in Inflammation (Percentage of CD14+ Monocytes Expressing CD16)
Period 2 Lab 2 (Week 28)
|
67.83 percentage of monocytes expressing CD16
Standard Deviation 13.23
|
59.78 percentage of monocytes expressing CD16
Standard Deviation 21.14
|
Adverse Events
Galantamine 8mg
Serious events: 1 serious events
Other events: 2 other events
Deaths: 1 deaths
Galantamine 16mg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Galantamine 24mg
Serious events: 2 serious events
Other events: 2 other events
Deaths: 0 deaths
Placebo
Serious events: 2 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Galantamine 8mg
n=52 participants at risk
This is a crossover study such that all participants receive both placebo and galantamine. Participants were randomized to receive galantamine first and placebo second.
This study follows the FDA-recommended dosing regimen for galantamine extended release (GAL ER). This group represents when individuals were on the 8 mg dose (whether it was the first or second period).
|
Galantamine 16mg
n=49 participants at risk
This is a crossover study such that all participants receive both placebo and galantamine. Participants were randomized to receive galantamine first and placebo second.
This study follows the FDA-recommended dosing regimen for galantamine extended release (GAL ER). This group represents when individuals were on the 16 mg dose (whether it was the first or second period).
|
Galantamine 24mg
n=48 participants at risk
This is a crossover study such that all participants receive both placebo and galantamine. Participants were randomized to receive galantamine first and placebo second.
This study follows the FDA-recommended dosing regimen for galantamine extended release (GAL ER). This group represents when individuals were on the 24 mg dose (whether it was the first or second period).
|
Placebo
n=47 participants at risk
This is a crossover study such that all participants receive both placebo and galantamine. Participants were randomized to receive galantamine first and placebo second.
This group represents when individuals were taking placebo (at any point in the study).
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Gastrointestinal Bleeding
|
0.00%
0/52 • 28 weeks: From the start of treatment through the end of treatment
The definitions used do not differ. Adverse event reporting was completed using a symptom checklist, listing all expected side effects for the study drug, which was administered at all study visits and included severity rating and description of the symptom. Participants were also given the opportunity to report any events that were not listed on the checklist, provide a severity rating and description.
|
0.00%
0/49 • 28 weeks: From the start of treatment through the end of treatment
The definitions used do not differ. Adverse event reporting was completed using a symptom checklist, listing all expected side effects for the study drug, which was administered at all study visits and included severity rating and description of the symptom. Participants were also given the opportunity to report any events that were not listed on the checklist, provide a severity rating and description.
|
2.1%
1/48 • Number of events 1 • 28 weeks: From the start of treatment through the end of treatment
The definitions used do not differ. Adverse event reporting was completed using a symptom checklist, listing all expected side effects for the study drug, which was administered at all study visits and included severity rating and description of the symptom. Participants were also given the opportunity to report any events that were not listed on the checklist, provide a severity rating and description.
|
2.1%
1/47 • Number of events 1 • 28 weeks: From the start of treatment through the end of treatment
The definitions used do not differ. Adverse event reporting was completed using a symptom checklist, listing all expected side effects for the study drug, which was administered at all study visits and included severity rating and description of the symptom. Participants were also given the opportunity to report any events that were not listed on the checklist, provide a severity rating and description.
|
|
Blood and lymphatic system disorders
Low Hemoglobin
|
0.00%
0/52 • 28 weeks: From the start of treatment through the end of treatment
The definitions used do not differ. Adverse event reporting was completed using a symptom checklist, listing all expected side effects for the study drug, which was administered at all study visits and included severity rating and description of the symptom. Participants were also given the opportunity to report any events that were not listed on the checklist, provide a severity rating and description.
|
0.00%
0/49 • 28 weeks: From the start of treatment through the end of treatment
The definitions used do not differ. Adverse event reporting was completed using a symptom checklist, listing all expected side effects for the study drug, which was administered at all study visits and included severity rating and description of the symptom. Participants were also given the opportunity to report any events that were not listed on the checklist, provide a severity rating and description.
|
2.1%
1/48 • Number of events 1 • 28 weeks: From the start of treatment through the end of treatment
The definitions used do not differ. Adverse event reporting was completed using a symptom checklist, listing all expected side effects for the study drug, which was administered at all study visits and included severity rating and description of the symptom. Participants were also given the opportunity to report any events that were not listed on the checklist, provide a severity rating and description.
|
0.00%
0/47 • 28 weeks: From the start of treatment through the end of treatment
The definitions used do not differ. Adverse event reporting was completed using a symptom checklist, listing all expected side effects for the study drug, which was administered at all study visits and included severity rating and description of the symptom. Participants were also given the opportunity to report any events that were not listed on the checklist, provide a severity rating and description.
|
|
Musculoskeletal and connective tissue disorders
Bone fracture
|
1.9%
1/52 • Number of events 1 • 28 weeks: From the start of treatment through the end of treatment
The definitions used do not differ. Adverse event reporting was completed using a symptom checklist, listing all expected side effects for the study drug, which was administered at all study visits and included severity rating and description of the symptom. Participants were also given the opportunity to report any events that were not listed on the checklist, provide a severity rating and description.
|
0.00%
0/49 • 28 weeks: From the start of treatment through the end of treatment
The definitions used do not differ. Adverse event reporting was completed using a symptom checklist, listing all expected side effects for the study drug, which was administered at all study visits and included severity rating and description of the symptom. Participants were also given the opportunity to report any events that were not listed on the checklist, provide a severity rating and description.
|
0.00%
0/48 • 28 weeks: From the start of treatment through the end of treatment
The definitions used do not differ. Adverse event reporting was completed using a symptom checklist, listing all expected side effects for the study drug, which was administered at all study visits and included severity rating and description of the symptom. Participants were also given the opportunity to report any events that were not listed on the checklist, provide a severity rating and description.
|
0.00%
0/47 • 28 weeks: From the start of treatment through the end of treatment
The definitions used do not differ. Adverse event reporting was completed using a symptom checklist, listing all expected side effects for the study drug, which was administered at all study visits and included severity rating and description of the symptom. Participants were also given the opportunity to report any events that were not listed on the checklist, provide a severity rating and description.
|
|
Musculoskeletal and connective tissue disorders
Pulled muscle
|
0.00%
0/52 • 28 weeks: From the start of treatment through the end of treatment
The definitions used do not differ. Adverse event reporting was completed using a symptom checklist, listing all expected side effects for the study drug, which was administered at all study visits and included severity rating and description of the symptom. Participants were also given the opportunity to report any events that were not listed on the checklist, provide a severity rating and description.
|
0.00%
0/49 • 28 weeks: From the start of treatment through the end of treatment
The definitions used do not differ. Adverse event reporting was completed using a symptom checklist, listing all expected side effects for the study drug, which was administered at all study visits and included severity rating and description of the symptom. Participants were also given the opportunity to report any events that were not listed on the checklist, provide a severity rating and description.
|
0.00%
0/48 • 28 weeks: From the start of treatment through the end of treatment
The definitions used do not differ. Adverse event reporting was completed using a symptom checklist, listing all expected side effects for the study drug, which was administered at all study visits and included severity rating and description of the symptom. Participants were also given the opportunity to report any events that were not listed on the checklist, provide a severity rating and description.
|
2.1%
1/47 • Number of events 1 • 28 weeks: From the start of treatment through the end of treatment
The definitions used do not differ. Adverse event reporting was completed using a symptom checklist, listing all expected side effects for the study drug, which was administered at all study visits and included severity rating and description of the symptom. Participants were also given the opportunity to report any events that were not listed on the checklist, provide a severity rating and description.
|
Other adverse events
| Measure |
Galantamine 8mg
n=52 participants at risk
This is a crossover study such that all participants receive both placebo and galantamine. Participants were randomized to receive galantamine first and placebo second.
This study follows the FDA-recommended dosing regimen for galantamine extended release (GAL ER). This group represents when individuals were on the 8 mg dose (whether it was the first or second period).
|
Galantamine 16mg
n=49 participants at risk
This is a crossover study such that all participants receive both placebo and galantamine. Participants were randomized to receive galantamine first and placebo second.
This study follows the FDA-recommended dosing regimen for galantamine extended release (GAL ER). This group represents when individuals were on the 16 mg dose (whether it was the first or second period).
|
Galantamine 24mg
n=48 participants at risk
This is a crossover study such that all participants receive both placebo and galantamine. Participants were randomized to receive galantamine first and placebo second.
This study follows the FDA-recommended dosing regimen for galantamine extended release (GAL ER). This group represents when individuals were on the 24 mg dose (whether it was the first or second period).
|
Placebo
n=47 participants at risk
This is a crossover study such that all participants receive both placebo and galantamine. Participants were randomized to receive galantamine first and placebo second.
This group represents when individuals were taking placebo (at any point in the study).
|
|---|---|---|---|---|
|
Psychiatric disorders
Depression
|
1.9%
1/52 • Number of events 1 • 28 weeks: From the start of treatment through the end of treatment
The definitions used do not differ. Adverse event reporting was completed using a symptom checklist, listing all expected side effects for the study drug, which was administered at all study visits and included severity rating and description of the symptom. Participants were also given the opportunity to report any events that were not listed on the checklist, provide a severity rating and description.
|
4.1%
2/49 • Number of events 2 • 28 weeks: From the start of treatment through the end of treatment
The definitions used do not differ. Adverse event reporting was completed using a symptom checklist, listing all expected side effects for the study drug, which was administered at all study visits and included severity rating and description of the symptom. Participants were also given the opportunity to report any events that were not listed on the checklist, provide a severity rating and description.
|
2.1%
1/48 • Number of events 1 • 28 weeks: From the start of treatment through the end of treatment
The definitions used do not differ. Adverse event reporting was completed using a symptom checklist, listing all expected side effects for the study drug, which was administered at all study visits and included severity rating and description of the symptom. Participants were also given the opportunity to report any events that were not listed on the checklist, provide a severity rating and description.
|
4.3%
2/47 • Number of events 2 • 28 weeks: From the start of treatment through the end of treatment
The definitions used do not differ. Adverse event reporting was completed using a symptom checklist, listing all expected side effects for the study drug, which was administered at all study visits and included severity rating and description of the symptom. Participants were also given the opportunity to report any events that were not listed on the checklist, provide a severity rating and description.
|
|
General disorders
Fatigue
|
1.9%
1/52 • Number of events 1 • 28 weeks: From the start of treatment through the end of treatment
The definitions used do not differ. Adverse event reporting was completed using a symptom checklist, listing all expected side effects for the study drug, which was administered at all study visits and included severity rating and description of the symptom. Participants were also given the opportunity to report any events that were not listed on the checklist, provide a severity rating and description.
|
8.2%
4/49 • Number of events 4 • 28 weeks: From the start of treatment through the end of treatment
The definitions used do not differ. Adverse event reporting was completed using a symptom checklist, listing all expected side effects for the study drug, which was administered at all study visits and included severity rating and description of the symptom. Participants were also given the opportunity to report any events that were not listed on the checklist, provide a severity rating and description.
|
2.1%
1/48 • Number of events 1 • 28 weeks: From the start of treatment through the end of treatment
The definitions used do not differ. Adverse event reporting was completed using a symptom checklist, listing all expected side effects for the study drug, which was administered at all study visits and included severity rating and description of the symptom. Participants were also given the opportunity to report any events that were not listed on the checklist, provide a severity rating and description.
|
2.1%
1/47 • Number of events 4 • 28 weeks: From the start of treatment through the end of treatment
The definitions used do not differ. Adverse event reporting was completed using a symptom checklist, listing all expected side effects for the study drug, which was administered at all study visits and included severity rating and description of the symptom. Participants were also given the opportunity to report any events that were not listed on the checklist, provide a severity rating and description.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/52 • 28 weeks: From the start of treatment through the end of treatment
The definitions used do not differ. Adverse event reporting was completed using a symptom checklist, listing all expected side effects for the study drug, which was administered at all study visits and included severity rating and description of the symptom. Participants were also given the opportunity to report any events that were not listed on the checklist, provide a severity rating and description.
|
0.00%
0/49 • 28 weeks: From the start of treatment through the end of treatment
The definitions used do not differ. Adverse event reporting was completed using a symptom checklist, listing all expected side effects for the study drug, which was administered at all study visits and included severity rating and description of the symptom. Participants were also given the opportunity to report any events that were not listed on the checklist, provide a severity rating and description.
|
0.00%
0/48 • 28 weeks: From the start of treatment through the end of treatment
The definitions used do not differ. Adverse event reporting was completed using a symptom checklist, listing all expected side effects for the study drug, which was administered at all study visits and included severity rating and description of the symptom. Participants were also given the opportunity to report any events that were not listed on the checklist, provide a severity rating and description.
|
4.3%
2/47 • Number of events 2 • 28 weeks: From the start of treatment through the end of treatment
The definitions used do not differ. Adverse event reporting was completed using a symptom checklist, listing all expected side effects for the study drug, which was administered at all study visits and included severity rating and description of the symptom. Participants were also given the opportunity to report any events that were not listed on the checklist, provide a severity rating and description.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place