Trial Outcomes & Findings for Resveratrol and Sirolimus in Lymphangioleiomyomatosis Trial (NCT NCT03253913)
NCT ID: NCT03253913
Last Updated: 2023-02-01
Results Overview
Change in serum VEGF-D level in pg/ml after treatment with a combination of resveratrol and sirolimus as compared to the historical VEGF-D level in patients on a stable dose of sirolimus alone. Baseline VEGF-D values represent serum VEGF-D levels on stable dose of sirolimus alone prior to starting study drug.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
25 participants
Primary outcome timeframe
Baseline, Week 8, Week 16, Week 24
Results posted on
2023-02-01
Participant Flow
Participant milestones
| Measure |
Treatment Arm
Resveratrol 250mg daily for the first 8 weeks, followed by 250mg twice daily for the next 8 weeks, and then 500mg twice daily for the last 8 weeks.
Patients will be on a stable background therapy of sirolimus prior to enrolling and will continue on that regimen throughout the study.
Sirolimus: Patients will be on a stable dose of sirolimus prior to enrolling and will continue that throughout the study.
Resveratrol: Escalating doses of resveratrol will be given throughout the study. Patients will start at 250mg daily for 8 weeks, followed by 500mg daily for 8 weeks, and 500mg BID for the last 8 weeks.
|
|---|---|
|
First 8 Weeks (250mg Daily Resveratrol)
STARTED
|
25
|
|
First 8 Weeks (250mg Daily Resveratrol)
COMPLETED
|
25
|
|
First 8 Weeks (250mg Daily Resveratrol)
NOT COMPLETED
|
0
|
|
Weeks 8 - 16 (Resveratrol 500mg Daily)
STARTED
|
25
|
|
Weeks 8 - 16 (Resveratrol 500mg Daily)
COMPLETED
|
25
|
|
Weeks 8 - 16 (Resveratrol 500mg Daily)
NOT COMPLETED
|
0
|
|
Weeks 16-24 (Resveratrol 1,000mg Daily)
STARTED
|
25
|
|
Weeks 16-24 (Resveratrol 1,000mg Daily)
COMPLETED
|
25
|
|
Weeks 16-24 (Resveratrol 1,000mg Daily)
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Resveratrol and Sirolimus in Lymphangioleiomyomatosis Trial
Baseline characteristics by cohort
| Measure |
Treatment Arm
n=25 Participants
Resveratrol 250mg daily for the first 8 weeks, followed by 250mg twice daily for the next 8 weeks, and then 500mg twice daily for the last 8 weeks.
Patients will be on a stable background therapy of sirolimus prior to enrolling and will continue on that regimen throughout the study.
Sirolimus: Patients will be on a stable dose of sirolimus prior to enrolling and will continue that throughout the study.
Resveratrol: Escalating doses of resveratrol will be given throughout the study. Patients will start at 250mg daily for 8 weeks, followed by 500mg daily for 8 weeks, and 500mg BID for the last 8 weeks.
|
|---|---|
|
Age, Continuous
|
51 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
25 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
25 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
23 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
25 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 8, Week 16, Week 24Population: Longitudinal slope of serum VEGF-D levels
Change in serum VEGF-D level in pg/ml after treatment with a combination of resveratrol and sirolimus as compared to the historical VEGF-D level in patients on a stable dose of sirolimus alone. Baseline VEGF-D values represent serum VEGF-D levels on stable dose of sirolimus alone prior to starting study drug.
Outcome measures
| Measure |
Treatment Arm
n=25 Participants
Resveratrol 250mg daily for the first 8 weeks, followed by 250mg twice daily for the next 8 weeks, and then 500mg twice daily for the last 8 weeks.
Patients will be on a stable background therapy of sirolimus prior to enrolling and will continue on that regimen throughout the study.
Sirolimus: Patients will be on a stable dose of sirolimus prior to enrolling and will continue that throughout the study.
Resveratrol: Escalating doses of resveratrol will be given throughout the study. Patients will start at 250mg daily for 8 weeks, followed by 500mg daily for 8 weeks, and 500mg BID for the last 8 weeks.
|
|---|---|
|
Serum Vascular Endothelial Growth Factor-D (VEGF-D) Levels After Treatment With a Combination of Resveratrol and Sirolimus as Compared to Baseline Serum VEGF-D Levels on Sirolimus Alone
Baseline VEGF-D level in patients on a stable dose of sirolimus alone
|
617 pg/ml
Interval 489.0 to 677.0
|
|
Serum Vascular Endothelial Growth Factor-D (VEGF-D) Levels After Treatment With a Combination of Resveratrol and Sirolimus as Compared to Baseline Serum VEGF-D Levels on Sirolimus Alone
Week 8
|
543 pg/ml
Interval 455.0 to 704.0
|
|
Serum Vascular Endothelial Growth Factor-D (VEGF-D) Levels After Treatment With a Combination of Resveratrol and Sirolimus as Compared to Baseline Serum VEGF-D Levels on Sirolimus Alone
Week 16
|
581 pg/ml
Interval 485.0 to 724.0
|
|
Serum Vascular Endothelial Growth Factor-D (VEGF-D) Levels After Treatment With a Combination of Resveratrol and Sirolimus as Compared to Baseline Serum VEGF-D Levels on Sirolimus Alone
Week 24
|
575 pg/ml
Interval 448.0 to 673.0
|
SECONDARY outcome
Timeframe: Baseline, Week 8, Week 16, Week 24Safety and adverse effect profile of combined resveratrol and sirolimus in adult patients with LAM
Outcome measures
| Measure |
Treatment Arm
n=25 Participants
Resveratrol 250mg daily for the first 8 weeks, followed by 250mg twice daily for the next 8 weeks, and then 500mg twice daily for the last 8 weeks.
Patients will be on a stable background therapy of sirolimus prior to enrolling and will continue on that regimen throughout the study.
Sirolimus: Patients will be on a stable dose of sirolimus prior to enrolling and will continue that throughout the study.
Resveratrol: Escalating doses of resveratrol will be given throughout the study. Patients will start at 250mg daily for 8 weeks, followed by 500mg daily for 8 weeks, and 500mg BID for the last 8 weeks.
|
|---|---|
|
Number of Treatment-Emergent Adverse Events
250 mg daily
|
42 Adverse effects
|
|
Number of Treatment-Emergent Adverse Events
500mg daily
|
25 Adverse effects
|
|
Number of Treatment-Emergent Adverse Events
1000mg daily
|
25 Adverse effects
|
SECONDARY outcome
Timeframe: Baseline, Week 8, Week 16, Week 24Difference in the absolute Forced expiratory volume in one-second (FEV1) after 24 weeks of treatment. FEV1 values reported are in liters. There are no definite minimum and maximum values of FEV1 as it is a physiological measure of lung function and varies from individual to individual. Higher FEV1 scores indicate better lung function.
Outcome measures
| Measure |
Treatment Arm
n=25 Participants
Resveratrol 250mg daily for the first 8 weeks, followed by 250mg twice daily for the next 8 weeks, and then 500mg twice daily for the last 8 weeks.
Patients will be on a stable background therapy of sirolimus prior to enrolling and will continue on that regimen throughout the study.
Sirolimus: Patients will be on a stable dose of sirolimus prior to enrolling and will continue that throughout the study.
Resveratrol: Escalating doses of resveratrol will be given throughout the study. Patients will start at 250mg daily for 8 weeks, followed by 500mg daily for 8 weeks, and 500mg BID for the last 8 weeks.
|
|---|---|
|
Change in Forced Expiratory Volume in One-second (FEV1) After 24 Weeks of Combined Treatment With Resveratrol and Sirolimus
Baseline
|
1.74 Absolute FEV1 in liters
Interval 1.46 to 2.3
|
|
Change in Forced Expiratory Volume in One-second (FEV1) After 24 Weeks of Combined Treatment With Resveratrol and Sirolimus
Week 8
|
1.98 Absolute FEV1 in liters
Interval 1.4 to 2.36
|
|
Change in Forced Expiratory Volume in One-second (FEV1) After 24 Weeks of Combined Treatment With Resveratrol and Sirolimus
Week 16
|
2.01 Absolute FEV1 in liters
Interval 1.18 to 2.57
|
|
Change in Forced Expiratory Volume in One-second (FEV1) After 24 Weeks of Combined Treatment With Resveratrol and Sirolimus
Week 24
|
1.94 Absolute FEV1 in liters
Interval 1.2 to 2.59
|
SECONDARY outcome
Timeframe: Baseline, Week 8, Week 16, Week 24.Quality of life scores will be calculated by using SGRQ to determine if the combination of resveratrol and sirolimus can improve the quality of life in patients with LAM. This is a disease-specific instrument designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease. Scores range from 0 to 100, with higher scores indicating worse quality of life.
Outcome measures
| Measure |
Treatment Arm
n=25 Participants
Resveratrol 250mg daily for the first 8 weeks, followed by 250mg twice daily for the next 8 weeks, and then 500mg twice daily for the last 8 weeks.
Patients will be on a stable background therapy of sirolimus prior to enrolling and will continue on that regimen throughout the study.
Sirolimus: Patients will be on a stable dose of sirolimus prior to enrolling and will continue that throughout the study.
Resveratrol: Escalating doses of resveratrol will be given throughout the study. Patients will start at 250mg daily for 8 weeks, followed by 500mg daily for 8 weeks, and 500mg BID for the last 8 weeks.
|
|---|---|
|
St. George's Respiratory Questionnaire (SGRQ) Quality of Life Assessment Scores After Treatment With Combined Resveratrol and Sirolimus
Baseline
|
42 score on a scale
Interval 39.0 to 46.0
|
|
St. George's Respiratory Questionnaire (SGRQ) Quality of Life Assessment Scores After Treatment With Combined Resveratrol and Sirolimus
Week 8
|
43.5 score on a scale
Interval 38.0 to 49.0
|
|
St. George's Respiratory Questionnaire (SGRQ) Quality of Life Assessment Scores After Treatment With Combined Resveratrol and Sirolimus
Week 16
|
43 score on a scale
Interval 40.0 to 49.0
|
|
St. George's Respiratory Questionnaire (SGRQ) Quality of Life Assessment Scores After Treatment With Combined Resveratrol and Sirolimus
Week 24
|
42 score on a scale
Interval 39.0 to 47.0
|
SECONDARY outcome
Timeframe: Baseline, Week 8, Week 16, Week 24Quality of life scores will be calculated by using ATAQ-LAM to determine if the combination of resveratrol and sirolimus can improve the quality of life in patients with LAM. A Tool to Assess Quality of Life in LAM (ATAQ-LAM) is a disease-specific instrument designed to assess HRQOL in patients with LAM, and consists of 32 items divided into 4 domains: exertional dyspnea, cough, fatigue, and emotional well-being. The total scores on this scale can range between 32 - 192, with higher scores indicating worse quality of life.
Outcome measures
| Measure |
Treatment Arm
n=25 Participants
Resveratrol 250mg daily for the first 8 weeks, followed by 250mg twice daily for the next 8 weeks, and then 500mg twice daily for the last 8 weeks.
Patients will be on a stable background therapy of sirolimus prior to enrolling and will continue on that regimen throughout the study.
Sirolimus: Patients will be on a stable dose of sirolimus prior to enrolling and will continue that throughout the study.
Resveratrol: Escalating doses of resveratrol will be given throughout the study. Patients will start at 250mg daily for 8 weeks, followed by 500mg daily for 8 weeks, and 500mg BID for the last 8 weeks.
|
|---|---|
|
Scores on "A Tool to Assess Quality of Life in LAM (ATAQ-LAM) Quality of Life Assessment" Scale After Treatment With 24 Weeks of Resveratrol and Sirolimus
Baseline
|
72 score on a scale
Interval 54.0 to 88.0
|
|
Scores on "A Tool to Assess Quality of Life in LAM (ATAQ-LAM) Quality of Life Assessment" Scale After Treatment With 24 Weeks of Resveratrol and Sirolimus
Week 8
|
70 score on a scale
Interval 49.0 to 101.0
|
|
Scores on "A Tool to Assess Quality of Life in LAM (ATAQ-LAM) Quality of Life Assessment" Scale After Treatment With 24 Weeks of Resveratrol and Sirolimus
Week 16
|
60 score on a scale
Interval 44.0 to 82.0
|
|
Scores on "A Tool to Assess Quality of Life in LAM (ATAQ-LAM) Quality of Life Assessment" Scale After Treatment With 24 Weeks of Resveratrol and Sirolimus
Week 24
|
57 score on a scale
Interval 47.0 to 87.0
|
SECONDARY outcome
Timeframe: Baseline, Week 8, Week 16, Week 24The San Diego shortness of breath questionnaire measures the quality-of-life impairment secondary to dyspnea resulting from pulmonary disorders. It is a 24-item measure that assesses self-reported shortness of breath while performing a variety of activities of daily living, with higher scores indicating worse quality of life.
Outcome measures
| Measure |
Treatment Arm
n=25 Participants
Resveratrol 250mg daily for the first 8 weeks, followed by 250mg twice daily for the next 8 weeks, and then 500mg twice daily for the last 8 weeks.
Patients will be on a stable background therapy of sirolimus prior to enrolling and will continue on that regimen throughout the study.
Sirolimus: Patients will be on a stable dose of sirolimus prior to enrolling and will continue that throughout the study.
Resveratrol: Escalating doses of resveratrol will be given throughout the study. Patients will start at 250mg daily for 8 weeks, followed by 500mg daily for 8 weeks, and 500mg BID for the last 8 weeks.
|
|---|---|
|
San Diego Shortness of Breath Score (SD-SOB) Quality of Life Assessment Scores After Treatment With 24 Weeks of Resveratrol and Sirolimus
Week 16
|
23 score on a scale
Interval 15.0 to 42.0
|
|
San Diego Shortness of Breath Score (SD-SOB) Quality of Life Assessment Scores After Treatment With 24 Weeks of Resveratrol and Sirolimus
Baseline
|
29 score on a scale
Interval 21.0 to 35.0
|
|
San Diego Shortness of Breath Score (SD-SOB) Quality of Life Assessment Scores After Treatment With 24 Weeks of Resveratrol and Sirolimus
Week 8
|
31 score on a scale
Interval 16.0 to 44.0
|
|
San Diego Shortness of Breath Score (SD-SOB) Quality of Life Assessment Scores After Treatment With 24 Weeks of Resveratrol and Sirolimus
Week 24
|
22 score on a scale
Interval 12.0 to 40.0
|
SECONDARY outcome
Timeframe: Baseline, Week 8, Week 16, Week 24The EuroQOL visual-analogue scale (EQVAS) measures self-reported ratings of health status. Scores range from 0 to100, with lower scores indicating worse functioning.
Outcome measures
| Measure |
Treatment Arm
n=25 Participants
Resveratrol 250mg daily for the first 8 weeks, followed by 250mg twice daily for the next 8 weeks, and then 500mg twice daily for the last 8 weeks.
Patients will be on a stable background therapy of sirolimus prior to enrolling and will continue on that regimen throughout the study.
Sirolimus: Patients will be on a stable dose of sirolimus prior to enrolling and will continue that throughout the study.
Resveratrol: Escalating doses of resveratrol will be given throughout the study. Patients will start at 250mg daily for 8 weeks, followed by 500mg daily for 8 weeks, and 500mg BID for the last 8 weeks.
|
|---|---|
|
EuroQOL Visual Analogue Scale (EQ-5D) Scores After Treatment With 24 Weeks of Sirolimus and Resveratrol.
Baseline
|
80 score on a scale
Interval 65.0 to 85.0
|
|
EuroQOL Visual Analogue Scale (EQ-5D) Scores After Treatment With 24 Weeks of Sirolimus and Resveratrol.
Week 8
|
85 score on a scale
Interval 75.0 to 90.0
|
|
EuroQOL Visual Analogue Scale (EQ-5D) Scores After Treatment With 24 Weeks of Sirolimus and Resveratrol.
Week 16
|
90 score on a scale
Interval 75.0 to 95.0
|
|
EuroQOL Visual Analogue Scale (EQ-5D) Scores After Treatment With 24 Weeks of Sirolimus and Resveratrol.
Week 24
|
90 score on a scale
Interval 80.0 to 90.0
|
Adverse Events
250mg Resveratrol Daily (First 8 Weeks)
Serious events: 0 serious events
Other events: 14 other events
Deaths: 0 deaths
500mg Daily Resveratrol (Weeks 8 - 16)
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
1,000mg Daily Resveratrol
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
250mg Resveratrol Daily (First 8 Weeks)
n=25 participants at risk
250mg resveratrol added to pre-existing sirolimus
|
500mg Daily Resveratrol (Weeks 8 - 16)
n=25 participants at risk
500mg resveratrol added to pre-existing sirolimus
|
1,000mg Daily Resveratrol
n=25 participants at risk
1,000mg resveratrol added to pre-existing sirolimus
|
|---|---|---|---|
|
Gastrointestinal disorders
nausea
|
12.0%
3/25 • Number of events 4 • 24 weeks
Adverse effects were tabulated using the National Cancer Institute's Common Terminology Criteria for Adverse Events version 4.
|
8.0%
2/25 • Number of events 2 • 24 weeks
Adverse effects were tabulated using the National Cancer Institute's Common Terminology Criteria for Adverse Events version 4.
|
8.0%
2/25 • Number of events 3 • 24 weeks
Adverse effects were tabulated using the National Cancer Institute's Common Terminology Criteria for Adverse Events version 4.
|
|
Gastrointestinal disorders
diarrhea
|
16.0%
4/25 • Number of events 4 • 24 weeks
Adverse effects were tabulated using the National Cancer Institute's Common Terminology Criteria for Adverse Events version 4.
|
4.0%
1/25 • Number of events 1 • 24 weeks
Adverse effects were tabulated using the National Cancer Institute's Common Terminology Criteria for Adverse Events version 4.
|
0.00%
0/25 • 24 weeks
Adverse effects were tabulated using the National Cancer Institute's Common Terminology Criteria for Adverse Events version 4.
|
|
Gastrointestinal disorders
gastrointestinal discomfort
|
12.0%
3/25 • Number of events 3 • 24 weeks
Adverse effects were tabulated using the National Cancer Institute's Common Terminology Criteria for Adverse Events version 4.
|
4.0%
1/25 • Number of events 2 • 24 weeks
Adverse effects were tabulated using the National Cancer Institute's Common Terminology Criteria for Adverse Events version 4.
|
12.0%
3/25 • Number of events 4 • 24 weeks
Adverse effects were tabulated using the National Cancer Institute's Common Terminology Criteria for Adverse Events version 4.
|
|
Infections and infestations
Infection
|
24.0%
6/25 • Number of events 7 • 24 weeks
Adverse effects were tabulated using the National Cancer Institute's Common Terminology Criteria for Adverse Events version 4.
|
4.0%
1/25 • Number of events 1 • 24 weeks
Adverse effects were tabulated using the National Cancer Institute's Common Terminology Criteria for Adverse Events version 4.
|
8.0%
2/25 • Number of events 2 • 24 weeks
Adverse effects were tabulated using the National Cancer Institute's Common Terminology Criteria for Adverse Events version 4.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place