Phase 2
N=25
Resveratrol and Sirolimus in Lymphangioleiomyomatosis Trial
Lymphangioleiomyomatosis
Bottom Line
View on ClinicalTrials.gov: NCT03253913 ↗Enrolled (actual)
25
Serious AEs
0.0%
Results posted
Feb 2023
Primary outcome: Primary: 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 — 617; 543; 581; 575 pg/ml
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Sirolimus (Drug); Resveratrol (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- Female
- Sponsor
- University of Cincinnati
- Primary completion
- Oct 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 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 |
617; 543; 581; 575 | — |
| SECONDARY Number of Treatment-Emergent Adverse Events |
42; 25; 25 | — |
| SECONDARY Change in Forced Expiratory Volume in One-second (FEV1) After 24 Weeks of Combined Treatment With Resveratrol and Sirolimus |
1.74; 1.98; 2.01; 1.94 | — |
| SECONDARY St. George's Respiratory Questionnaire (SGRQ) Quality of Life Assessment Scores After Treatment With Combined Resveratrol and Sirolimus |
42; 43.5; 43; 42 | — |
| SECONDARY 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 |
72; 70; 60; 57 | — |
| SECONDARY San Diego Shortness of Breath Score (SD-SOB) Quality of Life Assessment Scores After Treatment With 24 Weeks of Resveratrol and Sirolimus |
29; 31; 23; 22 | — |
| SECONDARY EuroQOL Visual Analogue Scale (EQ-5D) Scores After Treatment With 24 Weeks of Sirolimus and Resveratrol. |
80; 85; 90; 90 | — |
Summary
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.
Eligibility Criteria
Inclusion Criteria
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 biopsy (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.
- Age 18 years or greater.
- Signed and dated informed consent
- Currently on sirolimus for treatment of LAM for at least 20 weeks
- Evidence of disease stabilization on sirolimus as demonstrated by two stable values of serum VEGF-D post initiation of sirolimus drawn at least 12 weeks apart from each other. For the purpose of this study, a variation in serum VEGF-D of less than or equal to 15% is considered stable.
Exclusion Criteria
- Subjects who meet any of the following criteria are not eligible for enrollment as study participants:
- Known allergy or hypersensitivity to Resveratrol
- Inability to provide informed consent
- Active enrollment in other clinical drug trials for LAM
- Pregnant or plan to become pregnant in the next 6 months
- Breast feeding
- Inability to comply with pulmonary function tests or follow up visits
- Inadequate contraception
- Use of estrogen containing medications within the 30 days prior to randomization
- History of organ transplant
- Actively listed for lung transplantation
- Inability to comply with study procedures or attend scheduled study visits
- Any clinically significant medical disease (other than LAM) that is associated with an expected survival of less than 2 years, or likely to impact the ability of the patient to participate in the study in the opinion of the investigator, or impact the study efficacy or safety assessments.
Data sourced from ClinicalTrials.gov (NCT03253913). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.