The TRAIL Trial: A Research Study for Postmenopausal Women with Lymphangioleiomyomatosis (LAM)
What is the purpose of this study?
The TRAIL (Trial of Aromatase Inhibition in Lymphangioleiomyomatosis) Trial is a research study to find out if a medication called letrozole slows the rate
of decline in lung function in women with Lymphangioleiomyomatosis (LAM) when compared to a placebo. Letrozole is approved by the United States Food and Drug Administration to help prevent recurrence of breast cancer. The use of letrozole to treat LAM is experimental and has not been approved by the FDA.
Who will be included in this study?
Women 18 years and older who have LAM and are postmenopausal may be eligible to participate.
What is involved?
Women who enroll in the study will be involved for about one year. Participants will take either letrozole or a placebo every morning.
Those who are eligible to participate will be “randomized” by chance (like flipping a coin) into two groups. One group will receive the study medication; the other, a placebo (an inactive substance that looks like the study medication). There is an equal chance (50-50) of being placed into either group. Neither the study staff nor the study participants will know who is receiving the study medication and who is receiving the placebo.
In addition, participants will be asked to keep records of all medication they take during the study, including their assigned study medication/placebo and any prescription or over-the-counter medications.
All study-related medication, tests and exams that are not a normal part of routine care for LAM will be provided at no cost to participants. Tests and exams that are a normal part of routine care for LAM are the participant’s or the participant’s insurances company’s responsibility.
What are the benefits?
Participants may or may not benefit from participating in this study. Participants may benefit from the physical exams, pulmonary function tests, and other study procedures. Other potential benefits may include stabilization or improvement in lung function, and stabilization or decrease in the size of any kidney tumors or lymphangiomyomas. The information gained from this study may benefit other patients with LAM in the future.
Will I get all the facts about the study?
Those who are interested in participating will be given a consent form that thoroughly explains all of the details of the study. The form covers all of the procedures, the potential risks and benefits, who to contact with questions or concerns and more. A member of the study staff will review the consent form with participants to ensure all questions are answered. Study procedures will not begin until this form is signed.
What are the risks and discomforts of the study?
There may be some risks and discomforts, including potentially serious risks, involved with participation in the study. Letrozole is a widely used medication, and the safety profile is well understood. A detailed list of possible side effects will be provided to those interested in knowing more about this study.
Where and when will the study be done?
The study will be conducted in a subset of LAM Foundation Clinics. Sites for TRAIL will be chosen based on the number of interested and eligible patients in the region and the available resources for trials. The study is expected to enroll the first patient in March 2011 and to conclude in the fall of 2013.
Who should I contact for more participant information?
Stephanie Hartke, CRC
Who should I contact for more Investigator Information?
Frank McCormack, MD
Genome Wide Association Study (GWAS)
The LAM Foundation is excited to help with a very important research project. But we need your help to make this project successful. All you need to do is complete a 1 page questionnaire, sign a consent form, put a saliva sample into a special container that will be sent to you and then send it to the lab. This is all at no cost to you!
LAM Tissue Donation - How YOU Can Help
You can help LAM Foundation scientists become more knowledgeable about LAM by donating your tissue for LAM-related studies. To receive a packet of information describing the donation process, including consent and medical history forms, please contact the Private Donor Program at NDRI at email@example.com or by phone at 800.222.6374. You can also register online by clicking here.
If you are a LAM patient living in the United States:
History and Future Direction of LAM Tissue
Progress in LAM research is critically dependent on the availability of human tissues. The first report that LAM is due to mutations in tuberous sclerosis genes set the stage for trials and other advancements in LAM science. This was made possible by the availability of previously-archived biopsy specimens that were collected with the help of The LAM Foundation. The Foundation was the first to develop a system for LAM tissue collection from lung transplant patients.
In 1997, Sue Byrnes made contact with every LAM patient on transplant lists throughout the country, providing them with instructions and a set of vials for shipping transplant tissues to Dr. Teresa Smolarek's lab in Cincinnati. She assembled doctors who were interested in LAM tissue and corresponded with the lung transplant coordinator, pathology department, and surgical team at every transplant site - in most cases several times, as the patient ascended the transplant priority list and the time of transplant approached. Most sites were quite cooperative with dropping samples of lung tissue into the vials of fixatives provided and this system resulted in the collection of tissues from 20 transplants.
As interest in LAM research grew and investigators began to request varied methods of tissue preparation, remote coordination of tissue collection became inadequate. In 1998, Dr. Joel Moss, Gustavo Pacheco-Rodriguez and Connie Glascow from the National Heart, Lung, and Blood Institute (NHLBI) began to travel to transplant sites. In 2000, the Foundation hired a histologist, Marty Wallace of National Jewish Hospital (NJH), primarily to respond to requests for fresh LAM tissue, which he collected at the time of surgery and shipped directly from the site to the investigator. Sue's role remained much the same as it had been with Dr. Smolarek, preparing families, coordinators, and pathology departments for the big day, but upon receiving a page (she was also on call 24/7), she immediately notified Marty and Joel. The NHLBI and NJH teams would scramble for a last-minute flight at all hours of the day and night, and travel to the transplant site. Often, the strategy was to divide and conquer, with Marty leading the effort for the western United States and Dr. Moss' for the east coast. Joel and Marty were on call 24/7 for through 2003, and made a total of 136 and 70 trips to sites, respectively, and together, they stocked the NHLBI tissue bank with specimens from lung, blood, kidney and uterus. Over the years, these tissues have been distributed to dozens of investigators, and have been critical for several seminal discoveries, including the description of the genetic basis of LAM by Dr. Henske and the characterization of molecular targets for trials by Dr. Krymskaya.
Unfortunately, the funding for tissue distribution from the NHLBI tissue bank ran out in 2006 and to the frustration of all involved, the NIH system for requesting and receiving tissue became quite inefficient. The tissue bank was moved from the NHLBI to the National Disease Research Interchange (NDRI) in 2007. Although there are enough fixed tissues for decades of experiments, there remains a need for fresh tissue to develop LAM cell lines, and the methods for collecting and distributing this valuable resource are being refined by the NDRI. The continued generosity of patients is critical in this effort, and it is very important that the NDRI is informed of all pending surgeries and transplants. Together, the LAM community and the NLHBI have built a priceless resource that will produce scientific dividends long into the future.
Lung transplantation is not the answer to LAM; we need a cure. In the interim, lung transplantation, although highly risky, is the last resort for patients with end-stage LAM. Given the critical shortage of organs available for transplant, The LAM Foundation encourages all members of the LAM community to consider becoming an organ donor. The first step is to have a discussion with your family. If you wish to be an organ donor, remember to (1) sign your donor card and (2) notify your family of your wishes, so that precious gifts of life don't go unused.
If you would like to know more about organ donation, you may call your local Organ Procurement Office or visit one of many Web sites. The Second Wind Organization focuses on the needs of lung transplant recipients. Another excellent resource can be found at www.organdonor.gov. We hope that you will join with us in this tremendously important mission.