CRISP II STUDY The CRISP II (2) trial a continuation of the CRISP I trial is underway. The CRISP I study is completed; a study titled the Consortium of Renal Imaging Study
Project, a 5 center PKD study to discover the best parameter to follow for polycystic
kidney disease - is it MRI, ultrasound, kidney functioning or kidney
perfusion (the blood flow to the kidneys available through a specialized computer
program with an MRI imaging study). MRI measurements of renal blood flow is a marker in ADPKD. This determination paved the way for human clinical trials begun on the tail of this landmark finding.
The CRISP study also looked at the livers of the 241 participants. 90% of individuals with cystic kidneys also have liver cysts. With fine cross sectional MRI imaging, researchers were able to pick up very small liver cysts previously hidden deep within normal looking livers. With kidneys (different from liver cysts) it is the size and number of kidney cysts that correlates with disease progression.
According to Dr. Grantham: "CRISP showed that patients with the largest kidneys were the ones who had the fastest rates of kidney enlargement. In other words having large kidneys meant that the process had been going on at a relatively fast rate all of their lives. . . .kidney volume increase is an important factor in determining when renal insufficiency may develop." CRISP STUDY II (2) is a continuation of the original CRISP study, now called CRISP II, will follow the original patient cohort for an additional four years to study the relationship between kidney size and disease progression. Some patients may be in other studies as well but will continue to be monitored.
Crisp Study - complete articles:
CRISP - Magnetic Resonance measurements of renal blood flow
CRISP - Renal structure in early PKD
CRISP - Cyst number but not the rate of cystic growth is associated with PKD1 or PKD2 full article
CRISP - Cyst number but not the rate of cystic growth is associated with PKD1 or PKD2 abstract
CRISP - Article by Dr. Grantham
CRISP - Imaging progression in PKD
CRISP - Volume progression in PKD as an indicator of clinical outcomes
CRISP - MRI provides early alert as to progression of PKD
CRISP - Volume progression in PKD
HALT
PKD STUDY A
5 year PKD blood pressure study is recruiting to test if PKD'rs will benefit from tight strict control of blood pressure, which blood pressure medication benefits PKD'rs the most and which increases renal
perfusion. If you wish to be a participant In the HALT study, click here to go to their web site.
HALT PKD, a 5-year study on PKD blood pressure is recruiting. The medicines are listed here. It is set to begin at the following locations:
Beth Israel Deaconess Medical Center
Cleveland Clinic Foundation
Emory University
Mayo Clinic
Tufts-New England Medical Center
University of Colorado
University of Kansas Medical Center
Washington University in St. Louis
Download the patient
brochure
Download the physician
brochure
Clinical Trial HALT
OCTREOTIDE diminishes both liver and kidney cysts. Many of us may just want to wait and see how the trials come along. Octreotide Clinical trial is ongoing. This will be a double blind study. Two thirds of participants will receive the drug. Some known side effects are:
Sugar metabolism - If you have uncontrolled blood sugar, this may not be for you.
Gallstones - if you have a blockage of your ducts this may not be for you.
Allergy - if you are allergic to any of the components of Octreotide, this may not be for you.
Octreotide
Clinical Trial Octreotide
More info on Clinical Trial Octreotide
A completed clinical trial last year with Somatostatin Octreotide from Italy concluded that Octreotide was beneficial for diminishing kidney cysts. This next trial is a three year follow up trial at the Mario Negri Institute for Pharmacological Research, Bergamo, Italy. Contact Norberto Perico, M.D., at perico@marionegri.it
Clinical Trial Octreotide Italy
RAPAMUNE rapamycin sirolimus is a drug given for transplants. The Cleveland Clinic in the USA is considering clinical trials to see if it diminishes kidney cyst growth. Rapamune has some very serious side effects and diminishes only to kidney cysts. A prospective review of PKD transplant patients showed a 23% decrease in kidney cysts on a very small limited number of patients (I think it was 4). Rapamune is not to be taken lightly. However if one has had an organ transplant, it might be useful. Keep in mind it has no effect on liver cysts.
Clinical Trial Sirolimus
Cleveland Clinic
Clinical Trial Sirolimus University of Zurich
Clinical Trial Sirolimus and African American transplants
TOLVAPTAN is for those with Kidney Cysts. Clinical Trial Tolvaptan. Tolvaptan side effects include increased thirst and increased urine output 4-5 liters per day (quarts). Individuals taking tolvaptan must keep up with the fluid loss. It has been found safe and effective in congestive heart failure and cirrhosis of the liver.
TEMPO Phase II (2) the open label study, (every participant receives
tolvaptan) is well underway. In the double blind study phase III (3) some individuals receive tolvaptan others do not. The Inclusion - exclusion criteria for Tolvaptan Trials:
PKD, no other diseases
age 18 - 50 years of age
no other medications other than blood pressure
good kidney functioning - serum creatinine of 1.5 or less
Large kidney volume greater than 1000 cc. This third phase is to determine if Tolvaptan is effective in diminishing kidney cyst growth in humans with PKD polycystic kidney disease. For this 1000 to 3000 volunteers will be needed to complete the fast track FDA approval granted by the FDA. Tolvaptan, a vasopressin 2 blocking drug for polycystic kidney disease is useful for both ADPKD, the autosomal dominant version and ARPKD, the autosomal recessive version.
Tolvaptan (Otsuka Maryland Research Institute): Tolvaptan recently received fast track designation by the Food and Drug Administration because of its promise as a treatment for PKD. Tolvaptan a vasopressin inhibitor; a V2 Receptor blocker or a V2 drug. Surrounding kidney cysts is vasopressin and cyclic AMP. This triggers kidney cysts to fill with fluid, triggering kidney cyst expansion and growth. You may be wondering what can stimulate cyclic AMP to start this process
causing kidney cysts to expand, fill with fluid and to multiply in numbers?
Caffeine–caffeine from chocolate, de-caf coffee, de-caf tea, black
tea, green tea, white tea, coffee in all its forms and all other products
containing caffeine stimulates cyclic
AMP
With congestive heart failure diuretics are useful but can lead to kidney problems.
OPC 41061 or OPC 31026 (Tolvaptan) reduces fluid buildup, but it works differently from
diuretics. OPC 41061 impedes
the action of proteins in the kidney called vasopressin V2 receptors. These
molecules respond to the hormone vasopressin, which signals cells to take
up water. Blocking V2 receptors prevents fluid from accumulating. In addition
to keeping patients on the dry side, tolvaptan also appears to stabilize
salt imbalances, or hyponatremia (low sodium). Hyponatremia is an important
predictor of poor outcomes in heart failure patients. To date doctors have
no drugs to treat this condition -- a fact that could hasten the arrival
of tolvaptan. Common
side effects from OPC 31260 (the mother drug) are dry mouth, thirst, and increased
urination.
Possible things researchers will be looking at with Tolvaptan:
-Diminishes cyst fluid without damaging kidneys
-Increases urine production
-Enhanced renal blood flow
-Increased glomerular filtration rate (GFR)
-Decreased renal vascular resistance
-Reduction of renal cyclic AMP (increased by caffeine intake)
-Prevention of renal enlargement
-Protection of renal function
-Inhibition of kidney cyst growth
Another clinical trials presented at the American Heart Association's Scientific
Sessions 2003 compared the effects of tolvaptan and furosemide on renal
physiology and hemodynamics. In this study, the increased urine production
observed with tolvaptan appears to be associated with enhanced
renal blood flow, and glomerular filtration rate, and decreased renal vascular resistance. This second tolvaptan study was sponsored by Otsuka and conducted at the Mayo Clinic. Another clinical trial called the SALT trial. A third clinical trial about Heart Pressure and Tolvaptan.
Articles on Tolvaptan:
Clinical trials Tolvaptan
Effective treatment
Effectiveness of treatment
Chemical development
Inhibition of renal cysts
Fastrack status of Tolvaptan
A big thank you to any with an interest in participating. I hope to meet some of you at the Octreotide Trial. We can participate in only one clinical trial.
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In one drop of water are found all the secrets of all the oceans
-Kahil Gibran
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POLYCYSTIC LIVER DISEASE
OCTREOTIDE
PLD GENETIC STUDY
LIVER TRANSPLANT altruistic donors needed
PLD LIVER CYST RESEARCH
Octreotide - Somatostatin - Sandostatin LAR
Here is the latest paper on liver cysts and octreotide in animal studies. This trial is ongoing to test if liver cysts are lessened by a once monthly intramuscular injection of long acting octreotide. This is a first for us with liver cysts - a clinical trial to diminish liver cyst growth. To read more click here.
ADPLD GENETIC STUDY POLYCYSTIC LIVER DISEASE If you have no kidney cysts and only have liver cysts, this is probably ADPLD, autosomal dominant polycystic liver disease. For individuals without kidney cysts and only liver cysts, there is an ongoing study currently seeking participants. Your participation would help all of us with cystic liver disease. The researchers are Dr. Peter Harris, Dr Torres and Dr. Somlo. This requires a donation of a test tube of your blood. They can mail the kit to you and you mail it back in a pre-paid envelope. Email if you would like to participate giving your name, your contact information and that you would like information or to participate. An article on the gene discovered for ADPLD
PLD LIVER TRANPLANT Some individuals receive liver transplants for PLD polycystic liver disease. This is difficult to obtain as we with liver cysts rate low on the transplant list especially if we have only liver cysts. An article on PLD liver transplants; PLD treatments; PLD lists of avoids and useful; PLD and hormones; PLD and false estrogen; go to the topics page and peruse these pages and more at your leisure.
ALTRUISTIC Altruistic donors are needed. Please take a moment to read this article on ALTRUISTIC Donors. |
RESEARCH Update 2006 by Dr. Perrone. We are anticipating the release of several new treatments for cystic organ disease. Many of these latest research drugs are silently looming on the sidelines awaiting on the horizon of hope for the beginning or completion of clinical trials.
Clinical trials VLPD very low protein diet are ongoing in China:
1. Very low protein diet
2. EAA (essential amino acids)
3. ACE inhibitor
4. Alkalizer such as potassium or sodium citrate.
5. Control anemia
Tolvaptan diminishes kidney cyst growth. Rapamycin Rapamune Sirolimus is useful for kidney transplants and diminishes kidney cyst growth. Somatostatin diminishes liver cyst growth and diminishes kidney cyst growth. VLPD Very low protein diets coupled with ACE inhibitors, alkalizing agents, and EAA essential amino acids are a low cost means of delaying dialysis. Dialysis for end stage renal disease is too costly a bill for many countries of the world. New kidney transplant techniques hold promise for lowered post transplant maintenance cost.
No matter where you are with cystic organ disease - there is hope for a treatment specifically for you. If you are young, then diet might be something reasonable to try. If you have had a transplant, then Rapamycin holds promise. If you have expanding kidney cysts, Tolvaptan might do the trick. If you have expanding liver cysts, we are hopeful that somatostatin will prove helpful.
MORE ON RAPAMYCIN SIROLIMUS RAPAMUNE
This link is to a news article about Rapamycin Sirolimus Rapamune (same drug) from University of California in Santa and the Cleveland Clinic that prospectively looked at individuals with PKD kidney. Cleveland Clinic is thinking about a clinical trial with Rapamycin Rapamune Sirolimus. The person to contact for more information is Susan Wirth, BSN. This is an immunosuppressive drug that showed a 25% decrease kidney cysts in a small retrospective study done in Santa Barbara. In the animal model this is effective for diminishing kidney cyst growth.
Who knows, maybe those with a transplant who have retained their natives might be able to decrease kidney cyst size eventually reversing kidney cyst development?
Perhaps there is hope that in the distant future we might become like the little girl with the reversible heart transplant?
Rapamune reduced the size of kidney cysts by 25% in a prospective review.
From the CRISP study, they concluded that as kidney cysts increased in
size, kidney blood flow lessened. Kidney blood flow is the best
marker for testing if a treatment is working or not. Kidney blood flow
is assessed by an MRI of total kidney size cyst volume.
In animal studies they concluded that rapamycin prevents the loss of
kidney functioning.
Here is a study with human cells. Rapamycin interferes with mTOR
pathway, a target of ADPKD therapy.
Weimbs found that polycystin-1 controls a regulatory protein called
mTOR. A defect in polycystin-1 leads to over activation of mTOR. This
causes an excess growth of kidney cysts which destroy the kidney.
At Cleveland they are studying transplant patients who received
rapamycin.
Here is a site with pictures.
Inhibition of mTOR reverses renal cystogenesis in PKD
From the New England Journal of Medicine NIH sponsored CRISP study is using MRI assessment of the total kidney
volume as a primary outcome indicator. This is useful for evaluating if these treatments are effective early in the clinical trials. Another clinical trial with sirolimus: Use of Sirolimus vs.Tacrolimus for African-American transplants
University of Zurich Pilot study ADPKD and sirolimus You may directly email Dr. Andreas Serra, Principal Investigator, at andreas.serra@usz.ch
Articles on Rapamycin:
Clinical Trials Sirolimus
Rapamycin slows down disease
Discovery of Rapamycin
mTOR pathway
Prospective review of 4 cases
Inhibition of mTOR
Heart transplant reversed
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ADULT STEM CELL RESEARCH KIDNEY TRANSPLANT
Another article in the Gulf Times of India is on how to decrease the cost of post transplant medications by using adult stem cells. This takes the cost from $3000 per month to possibly $300 per month. The technique was developed by Dr. Trivedi, Ahmedabad, Gujarti India. H L Trivedi, returned to India from Canada in 1977 with the dream of developing an affordable treatment for kidney failure, has treated about 800 patients since his first transplant in 1998. He has published an abstract available at the pubmed website. This sounds similar to the work being done by Dr. Robert Montgomery at Johns Hopkins University with organ swapping to enable much more compatible kidney transplants with donors.
CLINICAL TRIALS PKD CHILDREN
The first study, to take place at The Children’s Hospital in Denver, will study how blood pressure medications can slow kidney and heart disease over a three year period in children and young adults with the dominant form of PKD. All expenses, including study-related medications, a home blood pressure machine, travel costs to and from Denver (including one parent to accompany minor children) and lab and radiology testing, will be provided. For more information, contact Dr. Melissa Cadnapaphornchai toll-free at 877-765-9297 or pkd.nurse@uchsc.edu.
The second study, with sites in both Boston and Kansas City, will evaluate children with chronic kidney disease, including those with the dominant and recessive forms of PKD, ADPKD and ARPKD. The study will determine the risk factors for kidney function decline and define how kidney failure impacts neurocognitive functions and behaviors, such as cardiovascular disease and growth failure. Click here. Study sites and contact information are as follows:
· Johns Hopkins University, Baltimore, MD: Susan Furth, M.D., Ph.D., sfurth@jhmi.edu or 410-502-7964 · Children’s Mercy Hospital, Kansas City, MO: Brad Warady, M.D., bwarady@cmh.edu or 816-234-3812
ARPKD Congenital Hepatic Fibrosis
This is open to children or adults with ARPKD/Congenital Hepatic Fibrosis with a kidney or liver transplant and stable graft function. Contact Dr. Meral Gunay at 301-594-4181 or by e-mail at mgaygun@nih.gov.
HEART DISEASE and PKD
This study is at Tufts-New England Medical Center and is directed to PKD patients in the Boston area. Those interested in participating, call Vandana Menon, M.D., Ph.D. at (617) 636-8791 or (617) 636-5895.
MORE CLINICAL TRIALS
ARPDK and Congenital Hepatic Fibrosis
SOMATOSTATIN kidney cyst 3 year follow Mario Negri Italy
SIROLIMUS RAPAMYCIN rapamune for PKD U of Zurich
SIROLIMUS RAPAMYCIN rapamune Cleveland Clinic
HALT PKD blood pressure 5 year study
BLOOD PRESSURE to slow progression ADPKD
TRANSPLANT registry U of Virginia
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I
HAVE PKD, WHAT CAN I DO
VLPD
Individuals with nephrotic syndrome can slow down their disease by beginning -
- Low Protein Diet dropping the protein to 0.6 or Very Low Protein - 0.3 grams/kg
- Eliminate animal proteins low nitrogen low phosphorus low sodium
- Essential amino acids supplements (Gambro or Calwood)
- ACE inhibitors or receptor site blockers for blood pressure control
- Alkalize i.e. sodium citrate, potassium citrate
- Correct anemia and take a few well chosen other supplements
For more information click here. An article Saving Failing Kidneys appeared in the Malaysian Star. |
last
updated:
Thu April 3, 2008
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