Trial Outcomes & Findings for Alendronate to Prevent Loss of Bronchoprotection in Asthma (NCT NCT02230332)
NCT ID: NCT02230332
Last Updated: 2018-01-12
Results Overview
Following administration of Salmeterol, the concentration of Methacholine required to produce a 20% drop in FEV1 - measured in mg/ml and reported on log base 2 scale.
COMPLETED
PHASE2/PHASE3
78 participants
8 weeks after randomization
2018-01-12
Participant Flow
Eligible participants were recruited from the community between January 2015 and May 2016 at 9 U.S. sites from the NHLBI AsthmaNet research network.
Participants with persistent asthma were first treated with fluticasone propionate 250mcg twice daily for 2 weeks during the run-in. Most of the participants who were not randomized did not meet the Salmeterol Protected Methacholine Challenge inclusion criterion.
Participant milestones
| Measure |
Alendronate
Alendronate in 10mg capsules taken once daily
Alendronate
|
Placebo
Placebo capsule taken once daily
Placebo
|
|---|---|---|
|
Overall Study
STARTED
|
38
|
40
|
|
Overall Study
COMPLETED
|
34
|
39
|
|
Overall Study
NOT COMPLETED
|
4
|
1
|
Reasons for withdrawal
| Measure |
Alendronate
Alendronate in 10mg capsules taken once daily
Alendronate
|
Placebo
Placebo capsule taken once daily
Placebo
|
|---|---|---|
|
Overall Study
Adverse Event
|
2
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
Protocol Violation
|
1
|
0
|
Baseline Characteristics
Alendronate to Prevent Loss of Bronchoprotection in Asthma
Baseline characteristics by cohort
| Measure |
Alendronate
n=38 Participants
Alendronate in 10mg capsules taken once daily
Alendronate
|
Placebo
n=40 Participants
Placebo capsule taken once daily
Placebo
|
Total
n=78 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
38.3 years
STANDARD_DEVIATION 13.1 • n=39 Participants
|
39.3 years
STANDARD_DEVIATION 12.3 • n=41 Participants
|
38.8 years
STANDARD_DEVIATION 12.6 • n=35 Participants
|
|
Sex: Female, Male
Female
|
20 Participants
n=39 Participants
|
27 Participants
n=41 Participants
|
47 Participants
n=35 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=39 Participants
|
13 Participants
n=41 Participants
|
31 Participants
n=35 Participants
|
|
Race/Ethnicity, Customized
White
|
24 Participants
n=39 Participants
|
21 Participants
n=41 Participants
|
45 Participants
n=35 Participants
|
|
Race/Ethnicity, Customized
Black
|
10 Participants
n=39 Participants
|
13 Participants
n=41 Participants
|
23 Participants
n=35 Participants
|
|
Race/Ethnicity, Customized
Asian/Pacific Islander
|
1 Participants
n=39 Participants
|
3 Participants
n=41 Participants
|
4 Participants
n=35 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latio
|
3 Participants
n=39 Participants
|
3 Participants
n=41 Participants
|
6 Participants
n=35 Participants
|
|
Region of Enrollment
United States
|
38 participants
n=39 Participants
|
40 participants
n=41 Participants
|
78 participants
n=35 Participants
|
|
Asthma Control Test score
|
21 units on a scale
n=39 Participants
|
21 units on a scale
n=41 Participants
|
21 units on a scale
n=35 Participants
|
|
FEV1 - percent of predicted
|
81.3 percent of predicted
STANDARD_DEVIATION 14.9 • n=39 Participants
|
83.1 percent of predicted
STANDARD_DEVIATION 14.0 • n=41 Participants
|
82.2 percent of predicted
STANDARD_DEVIATION 14.4 • n=35 Participants
|
|
Salmeterol Protected Methcholine PC20
|
5.4 mg/ml
STANDARD_DEVIATION 0.8 • n=39 Participants
|
3.7 mg/ml
STANDARD_DEVIATION 1 • n=41 Participants
|
4.5 mg/ml
STANDARD_DEVIATION 0.9 • n=35 Participants
|
PRIMARY outcome
Timeframe: 8 weeks after randomizationFollowing administration of Salmeterol, the concentration of Methacholine required to produce a 20% drop in FEV1 - measured in mg/ml and reported on log base 2 scale.
Outcome measures
| Measure |
Alendronate
n=34 Participants
Alendronate in 10mg capsules taken once daily
Alendronate
|
Placebo
n=39 Participants
Placebo capsule taken once daily
Placebo
|
|---|---|---|
|
Salmeterol Protected Methacholine Challenge PC20
|
1.8 mg/ml on log base 2 scale
Interval 1.1 to 2.5
|
1.7 mg/ml on log base 2 scale
Interval 1.1 to 2.3
|
SECONDARY outcome
Timeframe: 8 weeks after randomizationOutcome measures
| Measure |
Alendronate
n=34 Participants
Alendronate in 10mg capsules taken once daily
Alendronate
|
Placebo
n=39 Participants
Placebo capsule taken once daily
Placebo
|
|---|---|---|
|
Peripheral Blood Mononuclear Cell ADRB2 Cell Surface Density
|
1680 number of receptors per cell
Interval 1359.0 to 2076.0
|
1863 number of receptors per cell
Interval 1473.0 to 2358.0
|
SECONDARY outcome
Timeframe: 8 weeks after randomizationPeripheral blood mononuclear cells cAMP concentrations measured using isoproterenol (ISO) as a beta-2 adrenergic receptor agonist, and using phosphate buffered saline (PBS) as a positive control. The outcome is expressed as the ratio of cAMP concentration using ISO relative to cAMP concentration using PBS.
Outcome measures
| Measure |
Alendronate
n=34 Participants
Alendronate in 10mg capsules taken once daily
Alendronate
|
Placebo
n=39 Participants
Placebo capsule taken once daily
Placebo
|
|---|---|---|
|
Beta-2 Adrenergic Receptor Agonist-induced cAMP Production
|
5.9 ratio
Interval 4.7 to 7.5
|
5.9 ratio
Interval 4.9 to 7.2
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 8 weeks after randomizationSalivary Alpha Amylase (sAA) levels from saliva samples obtained through passive drooling, before and 1 hour after Salmeterol administration. The outcome is expressed as the ratio of the Post-Salmeterol to the Pre-Salmeterol sAA levels.
Outcome measures
| Measure |
Alendronate
n=34 Participants
Alendronate in 10mg capsules taken once daily
Alendronate
|
Placebo
n=39 Participants
Placebo capsule taken once daily
Placebo
|
|---|---|---|
|
Salivary Alpha Amylase Ratio (Post-Salmeterol / Pre-Salmeterol)
|
1.6 ratio
Interval 1.4 to 1.9
|
1.6 ratio
Interval 1.3 to 1.9
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 8 weeks after randomizationAsthma Control Test : Score calculated as the sum total of a 5-item questionnaire. Each item ranges from 1 (poor control) to 5 (good control) so that the range of the total score is 5 to 25. Scores below 20 indicate that asthma is not well controlled.
Outcome measures
| Measure |
Alendronate
n=34 Participants
Alendronate in 10mg capsules taken once daily
Alendronate
|
Placebo
n=39 Participants
Placebo capsule taken once daily
Placebo
|
|---|---|---|
|
Asthma Control Test (ACT)
|
22.2 units on a scale
Interval 21.2 to 23.2
|
22.2 units on a scale
Interval 21.4 to 23.1
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 8 weeks after randomizationOutcome measures
| Measure |
Alendronate
n=34 Participants
Alendronate in 10mg capsules taken once daily
Alendronate
|
Placebo
n=39 Participants
Placebo capsule taken once daily
Placebo
|
|---|---|---|
|
Fractional Exhaled Nitrix Oxide
|
16.8 parts per billion
Interval 12.9 to 21.9
|
15.4 parts per billion
Interval 11.7 to 20.1
|
Adverse Events
Alendronate
Placebo
Serious adverse events
| Measure |
Alendronate
n=38 participants at risk
Alendronate in 10mg capsules taken once daily
Alendronate
|
Placebo
n=40 participants at risk
Placebo capsule taken once daily
Placebo
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Viral Pneumonia
|
0.00%
0/38 • 8 weeks
|
2.5%
1/40 • Number of events 1 • 8 weeks
|
|
Gastrointestinal disorders
GI Bleed
|
0.00%
0/38 • 8 weeks
|
2.5%
1/40 • Number of events 1 • 8 weeks
|
Other adverse events
| Measure |
Alendronate
n=38 participants at risk
Alendronate in 10mg capsules taken once daily
Alendronate
|
Placebo
n=40 participants at risk
Placebo capsule taken once daily
Placebo
|
|---|---|---|
|
Gastrointestinal disorders
Esophageal reflux
|
5.3%
2/38 • Number of events 2 • 8 weeks
|
0.00%
0/40 • 8 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Acute nasopharyngitis
|
7.9%
3/38 • Number of events 4 • 8 weeks
|
5.0%
2/40 • Number of events 2 • 8 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Acute sinusitis
|
7.9%
3/38 • Number of events 3 • 8 weeks
|
0.00%
0/40 • 8 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Acue Upper Respiratory Infection
|
0.00%
0/38 • 8 weeks
|
10.0%
4/40 • Number of events 4 • 8 weeks
|
|
Respiratory, thoracic and mediastinal disorders
asthma exacerbation
|
0.00%
0/38 • 8 weeks
|
5.0%
2/40 • Number of events 3 • 8 weeks
|
|
Infections and infestations
thrush
|
0.00%
0/38 • 8 weeks
|
5.0%
2/40 • Number of events 2 • 8 weeks
|
|
General disorders
headache
|
5.3%
2/38 • Number of events 2 • 8 weeks
|
10.0%
4/40 • Number of events 5 • 8 weeks
|
|
General disorders
Heartburn
|
5.3%
2/38 • Number of events 2 • 8 weeks
|
0.00%
0/40 • 8 weeks
|
|
General disorders
Nausea alone
|
0.00%
0/38 • 8 weeks
|
7.5%
3/40 • Number of events 5 • 8 weeks
|
Additional Information
David Mauger, PhD
Penn State University Dept of Public Health Sciences
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place