Resveratrol and Sirolimus in Lymphangioleiomyomatosis Trial
Condition: Lymphangioleiomyomatosis
MeSH terms: Lymphangioleiomyomatosis
Intervention: Sirolimus; Resveratrol
Intervention description: Patients will have been on a stable dose of sirolimus prior to enrolling and will continue that throughout the study.; 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.
Intervention MeSH terms: Sirolimus; Resveratrol
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

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.

          1. 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.

          2. Age 18 years or greater.

          3. Signed and dated informed consent

          4. Currently on sirolimus for treatment of LAM for at least 20 weeks

          5. 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:

               1. Known allergy or hypersensitivity to Resveratrol

               2. Inability to provide informed consent

               3. Active enrollment in other clinical drug trials for LAM

               4. Pregnant or plan to become pregnant in the next 6 months

               5. Breast feeding

               6. Inability to comply with pulmonary function tests or follow up visits

               7. Inadequate contraception

               8. Use of estrogen containing medications within the 30 days prior to randomization

               9. History of organ transplant

              10. Actively listed for lung transplantation

              11. Inability to comply with study procedures or attend scheduled study visits

              12. 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.