Resveratrol and Sirolimus in Lymphangioleiomyomatosis Trial (RESULT)

Resveratrol and Sirolimus in Lymphangioleiomyomatosis Trial (RESULT)

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 Overview

• Status: Active, not recruiting
• Conditions: Lymphangioleiomyomatosis
• Intervention / Treatment: Drug: Sirolimus; Drug: Resveratrol

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Sirolimus; Patients will be on a stable dose of sirolimus prior to enrolling and will continue that throughout the study.; Other Names: Rapamycin; Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in serum VEGF-D level after treatment with a combination of resveratrol and sirolimus	Change in serum VEGF-D level in pg/ml after treatment with a combination of resveratrol and sirolimus as compared to the VEGF-D level in patients on a stable dose of sirolimus alone.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events	Safety and adverse effect profile of combined resveratrol and sirolimus in adult patients with LAM	24 weeks
Rate of change in Pulmonary function tests (PFTs) before and after treatment	Difference in the rate of change as well as absolute change in PFT parameters (Forced expiratory volume in one-second (FEV1), forced vital capacity (FVC), and diffusion capacity for carbon monoxide (DLCO)) will be measured after 24 weeks of treatment.	24 weeks
Difference in the St. George's Respiratory Questionnaire (SGRQ) quality of life assessment scores before and after treatment	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.	24 weeks
Difference in the A Tool to Assess Quality of Life in LAM (ATAQ-LAM) quality of life assessment scores before and after treatment	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.	24 weeks
Difference in the San Diego Shortness of Breath Score (SD-SOB) quality of life assessment scores before and after treatment	Quality of life scores will be calculated by using SD-SOB to determine if the combination of resveratrol and sirolimus can improve the quality of life in patients with LAM.	24 weeks
Difference in the EuroQOL visual analogue scale (EQ-5D) before and after treatment.	Quality of life scores will be calculated by using EQ-5D to determine if the combination of resveratrol and sirolimus can improve the quality of life in patients with LAM.	24 weeks

Collaborators and Investigators

• Sponsor: University of Cincinnati
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Nishant Gupta, MD, University of Cincinnati

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2018
• Primary Completion (Actual): October 15, 2022
• Study Completion (Anticipated): June 30, 2024

Study Registration Dates

• First Submitted: August 10, 2017
• First Submitted That Met QC Criteria: August 17, 2017
• First Posted (Actual): August 18, 2017

Study Record Updates

• Last Update Posted (Actual): October 21, 2022
• Last Update Submitted That Met QC Criteria: October 20, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphangiomyoma; Lymphatic Vessel Tumors; Perivascular Epithelioid Cell Neoplasms; Lymphangioleiomyomatosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Antioxidants; Sirolimus; Resveratrol
• Other Study ID Numbers: 2016-4904; 1R34HL138235-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No