Summary of Trials for Kidney Transplant Patients

KIDNEY TRANSPLANT PATIENTS 

Title: A Randomized, Placebo Controlled Double Blind Comparative Study Evaluating the Effect of Ramipril on Urinary Protein Excretion in Maintenance Renal Transplant Patients Converted to Sirolimus 

BIDMC Principal Investigator 
- Transplant Nephrologist, Didier Mandelbrot, MD 

Type of Study - Intervention: Phase IV Drug Trial 

Trial Status -Active and open to enrollment 

Sponsor - Pfizer 

BIDMC Contact Person: Meghan Ford: 617.632.9881 or mjford@bidmc.harvard.edu 

Why is This Study Being Done? - The purpose of this study is to learn whether the drug, ramipril, is safe and effective in preventing increased protein in the urine compared to placebo when anti-rejection medication is switched from a calcineurin inhibitor (cyclosporine or tacrolimus) to sirolimus. 

What's involved? - Kidney transplant patients are invited to participate in the study between 3 and 60 months following their kidney transplant. Study participants are randomized to take either ramipril or a placebo (inactive drug) prior to changing from the calcineurin inhibitor to sirolimus. Participants return to the Transplant Institute for about 15 visits for follow up over a one year period. Study visits are scheduled to coincide with routine clinic visits whenever possible. 

Find out More on the National Clinical Trials Registry: This study and other clinical trials are included in the National Clinical Trials Registry, which summarizes information about a clinical trial's purpose, who may participate, trial site locations, and contact phone numbers. Related research publications and study results are also posted to the Registry site as they become available. 

Use this link to read more about this study on the National Clinical Trials Registry: http://clinicaltrials.gov/ct2/show/NCT00502242 



Title: Study Evaluating A Planned Transition From Tacrolimus To Sirolimus In Kidney Transplant Recipients 

BIDMC Principal Investigator - Transplant Nephrologist, Didier Mandelbrot, MD 

Type of Study -Intervention: Phase IV Drug Trial 

Trial Status -Active, closed to enrollment 

Sponsor - Pfizer 

BIDMC Contact Person: Meghan Ford: 617.632.9881 or mjford@bidmc.harvard.edu 

Why Is This Study Being Done? - Tacrolimus is an anti rejection medication used with other medications to prevent rejection. Kidney transplant patients commonly start taking tacrolimus at the time of transplant and continued for the long term. Tacrolimus sometimes causes kidney scarring and scarring can sometimes lead to progressive failure of the transplanted kidney. Sirolimus is an anti rejection medication that is approved for use in reducing the potential for acute rejection in kidney transplant patients and may not cause chronic kidney damage over the long term. 

The purpose of this study is to evaluate whether using tacrolimus right after a transplant and then switching to sirolimus at 3 to 5 months after the transplant helps improve long-term kidney function. 

What's Involved? - Participants are invited to participate near the time of their kidney transplant. Patients who meet all of the eligibility criteria will be randomized 3-5 months after transplant (when their transplant physician agrees it is best) to either stay on tacrolimus or switch anti-rejection medication from tacrolimus to sirolimus. Study participants return to the Transplant Institute for about 12 visits for follow up over a two year period. Study visits are scheduled to coincide with routine clinic visits whenever possible. 

Find out More on the National Clinical Trials Registry: This study and other clinical trials are included in the National Clinical Trials Registry, which summarizes information about a clinical trial's purpose, who may participate, trial site locations, and contact phone numbers. Related research publications and study results are also posted to the Registry site as they become available. 

Use this link to read more about this study on the National Clinical Trials Registry: http://clinicaltrials.gov/ct2/show/NCT00895583 


Title: Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial - Extended Criteria Donors 

BIDMC Principal Investigator 
- Transplant Nephrologist, Martha Pavlakis, MD 

Type of Study - Intervention: Phase III Drug Trial 

Trial Status -Active, closed to enrollment 

Sponsor - Bristol-Myers Squibb 

BIDMC Contact Person: Yun Wang: 617.632.9941 or ywang9@bidmc.harvard.edu 

Why Is This Study Being Done? - This study is designed for kidney transplant patients who receive a kidney from an extended criteria donor (ECD). Though the acceptance of an ECD organ may shorten a patient's time on the transplant waiting list, ECD kidneys sometimes exhibit signs of renal dysfunction at the time of transplantation. Anti rejection drugs commonly used, tacrolimus and cyclosporine, can also cause kidney dysfunction. Belatacept is an immunosuppressant medication that is different than cyclosporine and tacrolimus. Belatacept has not been associated with kidney dysfunction and may be particularly beneficial in kidney transplant recipients of ECD organs.

The purpose of this study is to evaluate the effects of belatacept compared with cyclosporine on: 
1. Kidney transplant patient and organ survival and 
2. The preservation of kidney function. 

What's Involved? - Kidney transplant patients who are receiving a kidney from an extended criteria donor (ECD) are invited to participate on the day of their kidney transplant. Participants are randomized to receive belatacept or cyclosporine for maintenance immune suppression and complete study monitoring visits after their transplant. Follow up study visits continued up to 7 years. Study participants continue taking their assigned immunosuppression medication and return for monitoring visits. Physical exams and laboratory test are completed to monitor the participant's general health status, kidney function, signs of kidney rejection or infection. BIDMC participants randomized to belatacept have the study drug administered as a once-a-month infusion in BIDMC's Harvard-Thorndike General Clinical Research Center on the east campus. 

Find out More on the National Clinical Trials Registry: This study and other clinical trials are included in the National Clinical Trials Registry, which summarizes information about a clinical trial's purpose, who may participate, trial site locations, and contact phone numbers. Related research publications and study results are also posted to the Registry site as they become available. 

Use this link to read more about this study on the National Clinical Trials Registry: http://clinicaltrials.gov/ct2/show/NCT00114777 


Title: Effect of Fluoroquinolones on BK Viremia in the Renal Transplant Recipient, a Multi-Center Study 

BIDMC Principal Investigator - Transplant Nephrologist, Didier Mandelbrot, MD 

Type of Study - Intervention: Phase IV Drug Trial 

Trial Status -Active and open to enrollment 

Sponsor - Brigham and Women's Hospital 

BIDMC Contact Person: Susan McDermott, RN, MPH: 617.632.9841 or smcderm2@bidmc.harvard.edu 

Why Is This Study Being Done? - Kidney transplant patients are at risk of infection after their transplant because they take immunosuppressants (anti rejection) medication to prevent rejection of the transplanted organ. One type of viral infection that is commonly seen in kidney transplant patients is BK virus infection. BK viremia (BK virus in the blood) can increase the risk of infection or injury to the transplanted kidney (called nephropathy) which can lead to rejection of the new kidney. At this time, there is no single standard treatment for BK viremia that all doctors agree is best. 

Levofloxacin (a fluoroquinolone) has been approved by FDA for use in treating bacterial infections, such as urinary tract infections. There is some evidence from the research laboratory, and in a few human patients, that levofloxacin may be effective in treating BK viremia but this has never been studied in a clinical trial. 

The purpose of this study is to investigate if levofloxacin is effective for treatment of BK viremia in kidney transplant patients with the goal of improving long term functioning of the transplanted kidney. 

What's Involved? - Kidney transplant patient who show evidence of BK viremia after their kidney transplant may be eligible to participate in this trial. Study participants will be randomized to take either levofloxacin or placebo (inactive drug) for 30 days. Follow up study visits coincide with routine clinic visits for 6 months following study treatment. 

Find out More on the National Clinical Trials Registry: This study and other clinical trials are included in the National Clinical Trials Registry, which summarizes information about a clinical trial's purpose, who may participate, trial site locations, and contact phone numbers. Related research publications and study results are also posted to the Registry site as they become available. 

Use this link to read more about this study on the National Clinical Trials Registry: http://clinicaltrials.gov/ct2/show/NCT01034176 


Title: An Observational Study to Assess the Prevalence of a Tolerance Signature in Renal Transplant Recipients 

BIDMC Principal Investigator - Transplant Nephrologist, Martha Pavlakis, MD 

Type of Study - Observational Study 

Trial Status -Active, closed to enrollment 

Sponsor - National Institute of Allergy and Infectious Diseases 

BIDMC Contact Person: Yun Wang: 617.632.9941 or ywang9@bidmc.harvard.edu 

Why Is This Study Being Done? - Study Investigators want to understand why some kidney transplant patients develop a "tolerance" for their transplanted kidney without rejecting it while other kidney transplant patients do not. 

What is "Tolerance?" One of the most common complications of kidney transplantation is rejection of the new kidney. This occurs because the body's immune system tries to attack (or reject) the newly transplanted kidney. 

Transplant patients take "immunosuppressive" or "anti-rejection" medication to help prevent rejection of the transplanted kidney. When a transplant patient stops taking the anti-rejection medicines, their body almost always reject their transplanted kidney. However, in very, very rare cases, transplant patients who stop taking these drugs do not reject their kidney and the kidney keeps working. They are said at that point to "tolerate" the transplanted kidney, and this condition is referred to as "tolerance". Kidney transplant experts are studying why some transplant patients develop this tolerance after receiving their transplant, while most patients do not. 

Study Investigators previously conducted a study to look for common biological and genetic markers in the blood of a very few patients who were found to be "tolerant" and they discovered several markers they now refer to as the 'Tolerance Signature'. 
The purpose of this study is to look for the Tolerance Signature in the blood and urine of a larger number of kidney transplant recipients. The research goals are to see how many transplant recipients have these same markers and identify unique characteristics of tolerant kidney transplant recipients that differ from recipients who would reject their transplanted kidney if they stopped taking the immunosuppressive drugs. 
This information could then be used as a basis for designing future research studies and provide important insight into factors that contribute to the development of tolerance. 

What's Involved? - Kidney transplant patients between 1 and 5 years following the date of their transplant may be eligible to participate in this study. Study participants complete three study visits over a 2 year period. The visits are scheduled about 12 months apart at the time of participants routine check ups with the transplant nephrologist. Study staff review medical records and collect blood and urine specimens at each of the three study visits. 

Find out More on the National Clinical Trials Registry: This study and other clinical trials are included in the National Clinical Trials Registry, which summarizes information about a clinical trial's purpose, who may participate, trial site locations, and contact phone numbers. Related research publications and study results are also posted to the Registry site as they become available. 

Use this link to read more about this study on the National Clinical Trials Registry: http://clinicaltrials.gov/ct2/show/NCT01516177 


Title: B-Cell Depletion by Anti-CD20 (Rituximab) in Renal Allograft Recipients who Develop Early de novo Anti-HLA Alloantibodies will Result in Inhibition of Alloantibody Production and Attenuation of Chronic Humoral Rejection 

BIDMC Principal Investigator 
- Transplant Nephrologist, Martha Pavlakis, MD 

Type of Study - Intervention, Phase II Drug Trial 

Trial Status - Closed to enrollment, follow up complete. 

Sponsor - The National Institute of Allergy and Infectious Diseases (NIAID) 

BIDMC Contact Person: Susan McDermott, RN, MPH: 617.632.9841 or smcderm2@bidmc.harvard.edu 

Why Is This Study Being Done? -This trial was designed in two stages. The objective of the first stage was to determine if kidney transplant patients who do not have antibodies (cells that form to fight infection or reject a transplanted organ) to their donor organ before transplant develop antibodies to their donor organ after transplant. Patients who were between 3 to 36 months after transplant were invited to participate in Stage 1. Participants' blood was taken every three months and analyzed to check if antibodies were present. If antibodies developed, participants were invited to join Stage 2 of the trial. The objective of Stage 2 was to determine if the antibodies that developed harmed the kidney (caused rejection or kidney dysfunction) and if the removal of the antibodies using a medication called rituximab reduced the progression of kidney dysfunction. Rituximab is FDA approved to treat other diseases not related to transplantation. Using rituximab in transplant patients for the reduction of antibodies was not considered an approved use. 

What's Involved? - Stage 1 Participants returned to the Transplant Institute every three months for a blood draw to check if antibodies have developed since the last check. If antibodies develop the participant was invited to join Stage 2. Stage 2 participants receive 2 doses of rituximab as an intravenous injection at 2 visits, 2 weeks apart. Participants then return for 5 follow up study monitoring visits over a 12 month period for checks on overall health status, kidney function, signs of rejection, or infection. Study visits were scheduled to coincide with routine clinic visits whenever possible. 

Find out More on the National Clinical Trials Registry: This study and other clinical trials are included in the National Clinical Trials Registry, which summarizes information about a clinical trial's purpose, who may participate, trial site locations, and contact phone numbers. Related research publications and study results are also posted to the Registry site as they become available. 

Use this link to read more about this study on the National Clinical Trials Registry: http://clinicaltrials.gov/ct2/show/NCT00307125 


Title: Complement Regulation and Renal Disease 

BIDMC Principal Investigator - Transplant Nephrologist, Martha Pavlakis, MD 

Type of Study - Genetic Family Tree Observational Study 

Trial Status - Active, enrollment limited to members of a single family plus 7 'healthy control participants' who have completed a workup for kidney donation 

Sponsor - This is a study that is initiated by the Investigator using funds provided by a donation from a "Grateful Patient" 

BIDMC Contact Person: Susan McDermott, RN, MPH: 617.632.9841 or smcderm2@bidmc.harvard.edu 

Why is This Study Being Done? - This study is about the genetic disorder called Complement Factor H Mutation. Some people with this genetic disorder develop serious health problems, such as kidney disease and vision problems, while others do not. Factor H mutation is a very rare genetic disorder that is known to run in families. 

We are now completing a study of the family of a Transplant Institute patient with chronic kidney disease caused by the Complement Factor H mutation. The main purpose of this study is to better understand why some people with this disorder become ill when others do not. 

With medical and genetic information from many individuals in the same family tree, we can identify family members who have the mutation, members who don't have the mutation and then learn more about the health difference between these individuals. We also hope to learn about any special circumstances that lead some individuals with the mutation to become ill while others seem not to develop illnesses commonly associated with Complete Factor H mutation. Although this is a study of only one family, what we learn may help physicians plan for future research studies of this and other types of Complement Factor disorders. 

What's Involved? - The patient and family members come to the Transplant Institute to have a brief physical exam and a blood sample is drawn. The blood samples are sent to special labs in Iowa and Germany so that the genetic testing can be completed. It takes 6 months for the labs to complete all the testing. After testing is complete, participants return to the Transplant Institute to see Dr. Pavlakis and discuss the results of the tests. 

We are also inviting 7 healthy people to volunteer to also give blood sample to use as 'healthy control subjects' for the study. In a clinical research study, a 'healthy control subject' is a person who does not have the disorder or disease being studied. Results from healthy controls are compared to results from the group being studied. The healthy control volunteers are identified from among the people who complete an evaluation at the Transplant Institute to serve as kidney donors.