A Phase 2 interventional study of Sirolimus and Resveratrol in Lymphangioleiomyomatosis, sponsored by University of Cincinnati. Completed at 1 site in United States. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-02-01.
Sponsored by University of Cincinnati · Phase 2, Interventional, and Treatment
Among 28 studies in Lymphangioleiomyomatosis with a site in United States — 6 open to participants now, 8 under way, 1 of them phase 3. Lymphangioleiomyomatosis · United States.
Among the 28 studies in Lymphangioleiomyomatosis with a site in United States, this one is the 9th largest by enrollment of the 21 interventional ones, is one of 3 that started in 2018, is one of 8 in phase 2, and was the 22nd registered.
49 studies on the registry are indexed under Lymphangioleiomyomatosis; 11 are open to participants now.
This study's enrollment of 25 is close to the median of 25 across 30 interventional studies indexed under Lymphangioleiomyomatosis.
Browse Lymphangioleiomyomatosis studies →6 of the 28 studies in Lymphangioleiomyomatosis with a site in United States are open now, in 2 countries. Each count lists the studies.
Of the 10 Lymphangioleiomyomatosis studies recruiting now, 6 (60%) set no upper age limit and 1 (10%) stop at 75 or younger; 4 take children under 18; 1 take healthy volunteers.
This study: 18 Years and older · female · no healthy volunteers.
The full table on the hub →28 studies; the count open now beside each. This study's row is marked.
First in 1995; this study’s year is marked. 3 started in 2018.
Median enrollment 24 across the 21 interventional studies, 400 across the 7 observational. Of the 20 that completed or were terminated, 12 (60%) have results posted.
2 of 28 have an industry lead sponsor. The 10 most frequent:
University of Cincinnati is the lead sponsor of 324 studies on the registry; 42 are open to participants now.
Of its 24 completed or terminated interventional studies of FDA-regulated products, 15 (63%) have results posted.
University of Cincinnati has 5 studies filed under Lymphangioleiomyomatosis — fewer than ten, so there is no comparison to draw.
2 of the studies in Lymphangioleiomyomatosis with a site in United States that are under way reach primary completion within a year, 0 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT06889168Columbia UniversityEvaluating the Long-term Safety and Tolerability of Imatinib in Patients With Lymphangioleiomyomatosis (LAM) | 2026-12 |
| NCT01799538National Heart, Lung, and Blood Institute (NHLBI)Nebulized or Inhaled Albuterol for Lymphangioleiomyomatosis | 2027-11-01 |
Among the 28 studies in Lymphangioleiomyomatosis with a site in United States, from their registry updates:
RESULT is a phase II dose-escalating, open-label, safety and efficacy study to determine if there is a potential benefit of resveratrol in combination with sirolimus in patients with lymphangioleiomyomatosis (LAM). The primary study objective is to assess the change in serum vascular endothelial growth factor-D (VEGF-D) level after 24 weeks of treatment with a combination of resveratrol and sirolimus as compared to the VEGF-D level in patients on a stable dose of sirolimus alone. The secondary objectives of this study include an assessment of the safety and adverse effect profile of combined resveratrol and sirolimus in adult patients with LAM, and to determine the effect of treatment with a combination of resveratrol and sirolimus on changes in lung function and quality of life.
Study Design RESULT was an open label, dose-escalation, phase 2 study with longitudinal repeated measures. In order to be eligible for trial inclusion, patients had to satisfy all of the following criteria: 1) confirmed diagnosis of LAM per the American Thoracic Society/Japanese Respiratory Society Clinical Practice Guidelines14, 2) age ≥18 years with signed informed consent, 3) on sirolimus for at least 20 weeks, and 4) VEGF-D stabilization as demonstrated by two stable values post initiation of sirolimus and drawn at least 12 weeks apart from each other. Key exclusion criteria included inability to provide consent, active listing for lung transplantation, enrolled in another interventional clinical trial, known allergy or hypersensitivity to resveratrol, and current or planned pregnancy in the next six months.
RESULT was a single site study conducted at the University of Cincinnati (UC). Study enrollment was open to LAM patients throughout the United States with travel reimbursement provided through the study. The study was reviewed and approved by UC's Institutional Review Board (IRB 2016-4904). An independent Data and Safety Monitoring Board (DSMB) was convened and met every six months to ensure the safety of study participants. All subjects provided written informed consent prior to the conduct of any study related activity.
Outcome Measures The primary objective of this study was to assess the change in serum VEGF-D value after 24 weeks of treatment with a combination of resveratrol and sirolimus, as compared to the historical VEGF-D values of patients prior to the study on sirolimus alone. Serial assessments of serum VEGF-D, pulmonary function tests (PFTs), treatment related adverse effects (AEs), complete blood count, liver and renal function tests, and HRQOL were performed at baseline and at 8, 16, and 24 weeks. In addition, sirolimus trough levels, measured 24 +/- 4 hours following the last dose, were assessed at baseline and at weeks 2, 4, 8, 12, 16, 18, 20 and 24. VEGF-D quantification was performed at the Translational Trial Development and Support Laboratory based at Cincinnati Children's Hospital Medical Center in a College of American Pathologists (CAP)/Clinical Laboratory Improvement Amendments (CLIA) approved manner. All other laboratory assessments were performed via Quest Diagnostics. HRQOL was measured by using four validated scales: St. George's Respiratory Questionnaire (SGRQ), University of California San Diego Shortness of Breath score (SDSOB), EuroQol visual analogue scale (EQVAS), and A Tool to Assess Quality of Life in LAM (ATAQ-LAM).
Study Drug Resveratrol used in this study was obtained from Evolva and manufactured by fermentation using genetically modified yeast in a process that results in trans-resveratrol with a purity of at least 98%, and packaged into capsules with each capsule containing 125mg resveratrol. The capsules were independently verified for content by mass spectrometry performed at UC and for sterility by microbial testing at Q Laboratories Inc., Cincinnati. Investigational new drug (IND) designation for studying Resveratrol in this trial was obtained from the United States Food and Drug Administration (FDA): IND 131722; IND Sponsor: N. Gupta.
Resveratrol was administered in a stepwise dose escalating fashion at 8-week intervals with assessment of VEGF-D, PFTs, AEs, and HRQOL prior to each dose escalation. The starting dose of resveratrol was 250mg once daily for the first 8 weeks, followed by 500mg daily from Weeks 8 - 16, and 500mg twice daily for the last 8 weeks (Weeks 16 - 24), with provisions for dose reduction if necessitated by AEs. Treatment related AEs were tabulated using the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) version 4.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Subjects enrolled in the trial must meet all of the following criteria.
Definitive diagnosis LAM based on the presence of characteristic cystic change on high-resolution computed tomography (HRCT) of the chest. The diagnosis must be confirmed by one of the following:
A) Histopathological confirmation by (lung, abdominal mass, lymph node or kidney or cytology from thoracic or abdominal sources revealing human melanoma black-45 (HMB45)+ staining of spindled/epithelioid cells) B) Compatible chest CT scan findings in the setting of tuberous sclerosis, angiomyolipomas (diagnosed by CT, magnetic resonance imaging (MRI) by the site radiologist or biopsy) or chylous pleural effusion (verified by tap) C) Chest CT scan findings compatible with LAM and a VEGF-D level ≥ 800pg/ml.
Exclusion Criteria:
Subjects who meet any of the following criteria are not eligible for enrollment as study participants:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Drug: Sirolimus · Drug: Resveratrol
Patients will have been on a stable dose of sirolimus prior to enrolling and will continue that throughout the study.
Also known as: Rapamycin
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
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.
Time frame: Baseline, Week 8, Week 16, Week 24
Number of Treatment-Emergent Adverse Events
Safety and adverse effect profile of combined resveratrol and sirolimus in adult patients with LAM
Time frame: Baseline, Week 8, Week 16, Week 24
Change in Forced Expiratory Volume in One-second (FEV1) After 24 Weeks of Combined Treatment With Resveratrol and Sirolimus
Difference 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.
Time frame: Baseline, Week 8, Week 16, Week 24
St. George's Respiratory Questionnaire (SGRQ) Quality of Life Assessment Scores After Treatment With Combined Resveratrol and Sirolimus
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.
Time frame: Baseline, Week 8, Week 16, Week 24.
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
Quality 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.
Time frame: Baseline, Week 8, Week 16, Week 24
San Diego Shortness of Breath Score (SD-SOB) Quality of Life Assessment Scores After Treatment With 24 Weeks of Resveratrol and Sirolimus
The 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.
Time frame: Baseline, Week 8, Week 16, Week 24
EuroQOL Visual Analogue Scale (EQ-5D) Scores After Treatment With 24 Weeks of Sirolimus and Resveratrol.
The EuroQOL visual-analogue scale (EQVAS) measures self-reported ratings of health status. Scores range from 0 to100, with lower scores indicating worse functioning.
Time frame: Baseline, Week 8, Week 16, Week 24
| Milestone | Treatment Arm |
|---|---|
| Started | 25 |
| Completed | 25 |
| Not completed | 0 |
| Milestone | Treatment Arm |
|---|---|
| Started | 25 |
| Completed | 25 |
| Not completed | 0 |
| Milestone | Treatment Arm |
|---|---|
| Started | 25 |
| Completed | 25 |
| Not completed | 0 |
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.
| pg/ml | Treatment Arm |
|---|---|
| Baseline VEGF-D level in patients on a stable dose of sirolimus alone | 617 (489 to 677) |
| Week 8 | 543 (455 to 704) |
| Week 16 | 581 (485 to 724) |
| Week 24 | 575 (448 to 673) |
Safety and adverse effect profile of combined resveratrol and sirolimus in adult patients with LAM
| Adverse effects | Treatment Arm |
|---|---|
| 250 mg daily | 42 |
| 500mg daily | 25 |
| 1000mg daily | 25 |
Difference 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.
| Absolute FEV1 in liters | Treatment Arm |
|---|---|
| Baseline | 1.74 (1.46 to 2.3) |
| Week 8 | 1.98 (1.4 to 2.36) |
| Week 16 | 2.01 (1.18 to 2.57) |
| Week 24 | 1.94 (1.2 to 2.59) |
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.
| score on a scale | Treatment Arm |
|---|---|
| Baseline | 42 (39 to 46) |
| Week 8 | 43.5 (38 to 49) |
| Week 16 | 43 (40 to 49) |
| Week 24 | 42 (39 to 47) |
Quality 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.
| score on a scale | Treatment Arm |
|---|---|
| Baseline | 72 (54 to 88) |
| Week 8 | 70 (49 to 101) |
| Week 16 | 60 (44 to 82) |
| Week 24 | 57 (47 to 87) |
The 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.
| score on a scale | Treatment Arm |
|---|---|
| Baseline | 29 (21 to 35) |
| Week 8 | 31 (16 to 44) |
| Week 16 | 23 (15 to 42) |
| Week 24 | 22 (12 to 40) |
The EuroQOL visual-analogue scale (EQVAS) measures self-reported ratings of health status. Scores range from 0 to100, with lower scores indicating worse functioning.
| score on a scale | Treatment Arm |
|---|---|
| Baseline | 80 (65 to 85) |
| Week 8 | 85 (75 to 90) |
| Week 16 | 90 (75 to 95) |
| Week 24 | 90 (80 to 90) |
Collected over 24 weeks. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| 250mg Resveratrol Daily (First 8 Weeks) | 0/25 (0%) | 0/25 (0%) | 14/25 (56%) |
| 500mg Daily Resveratrol (Weeks 8 - 16) | 0/25 (0%) | 0/25 (0%) | 5/25 (20%) |
| 1,000mg Daily Resveratrol | 0/25 (0%) | 0/25 (0%) | 6/25 (24%) |
| Event | 250mg Resveratrol Daily (First 8 Weeks) | 500mg Daily Resveratrol (Weeks 8 - 16) | 1,000mg Daily Resveratrol |
|---|---|---|---|
| InfectionInfections and infestations | 6/25 | 1/25 | 2/25 |
| diarrheaGastrointestinal disorders | 4/25 | 1/25 | 0/25 |
| nauseaGastrointestinal disorders | 3/25 | 2/25 | 2/25 |
| gastrointestinal discomfortGastrointestinal disorders | 3/25 | 1/25 | 3/25 |
| Age, Continuous(years) | Treatment Arm |
|---|---|
| Median | 51 (47 to 58) |
| Sex: Female, Male(Participants) | Treatment Arm |
|---|---|
| Female | 25 |
| Male | 0 |
| Ethnicity (NIH/OMB)(Participants) | Treatment Arm |
|---|---|
| Hispanic or Latino | 0 |
| Not Hispanic or Latino | 25 |
| Unknown or Not Reported | 0 |
| Race (NIH/OMB)(Participants) | Treatment Arm |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 2 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 0 |
| White | 23 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
| Region of Enrollment(participants) | Treatment Arm |
|---|---|
| United States | 25 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No
Ran from Mar 2018 to primary completion in Oct 2022, 54 months.
Results were first posted in Feb 2023, 3 months after primary completion.
How these figures are worked out, and which studies are left out of them.
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Studies of the drugs tested here: Sirolimus · Resveratrol