Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT03253913 |
Other study ID # |
2016-4904 |
Secondary ID |
1R34HL138235-01 |
Status |
Completed |
Phase |
Phase 2
|
First received |
|
Last updated |
|
Start date |
March 31, 2018 |
Est. completion date |
October 15, 2022 |
Study information
Verified date |
January 2023 |
Source |
University of Cincinnati |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial 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.
Description:
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.