Resveratrol and Sirolimus in Lymphangioleiomyomatosis Trial

NCT03253913 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2016-49041R34HL138235-01
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Lymphangioleiomyomatosis

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline, Week 8, Week 16, Week 24

Secondary Outcomes (6)

• Number of Treatment-Emergent Adverse Events

  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

  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

  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

  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

  Baseline, Week 8, Week 16, Week 24

Study Arms (1)

Treatment Arm

EXPERIMENTAL

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

Interventions

Sirolimus DRUG

Patients will have been on a stable dose of sirolimus prior to enrolling and will continue that throughout the study.

Also known as: Rapamycin

Treatment Arm

Resveratrol DRUG

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.

Treatment Arm

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: LAM is a disease that almost exclusively involves females. Thus trial participants will be females only.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Cincinnati: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

Related Publications (1)

• Gupta N, Zhang B, Zhou Y, McCormack FX, Ingledue R, Robbins N, Kopras EJ, McMahan S, Singla A, Swigris J, Cole AG, Holz MK. Safety and Efficacy of Combined Resveratrol and Sirolimus in Lymphangioleiomyomatosis. Chest. 2023 May;163(5):1144-1155. doi: 10.1016/j.chest.2023.01.007. Epub 2023 Jan 13.

  PMID: 36642366 DERIVED

MeSH Terms

Conditions

Lymphangioleiomyomatosis

Interventions

Sirolimus; Resveratrol

Condition Hierarchy (Ancestors)

Lymphangiomyoma; Neoplasm, Lymphatic Tissue; Neoplasms by Histologic Type; Neoplasms; Perivascular Epithelioid Cell Neoplasms; Neoplasms, Connective and Soft Tissue; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Stilbestrols; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polyphenols; Phenols

Results Point of Contact

• Title: Nishant Gupta, MD
• Organization: University of Cincinnati

nishant.gupta@uc.edu

5135584831

Study Officials

• Nishant Gupta, MD

  University of Cincinnati

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Adjunct Assistant Professor

Study Record Dates

• First Submitted: August 10, 2017
• First Posted: August 18, 2017
• Study Start: March 31, 2018
• Primary Completion: October 15, 2022
• Study Completion: October 15, 2022
• Last Updated: February 1, 2023
• Results First Posted: February 1, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)