PLD Clinical Trials

Some PLD Trials

A Listing for a few PLD trials With Some Trial Results Available

Polycystic Liver Disease Questionnaire
Pasireotide LAR in severe Polycystic Liver Disease
Efficacy of Combining Pasireotide with Aspiration Sclerotherapy to Improve Volume Reduction of Hepatic Cysts
Hepatic Cyst Infection Following Sclerotherapy
Clinical and Molecular Investigations Into Ciliopathies
Sirolimus for Massive Polycystic Liver
Transplant Patient Registry of Liver, Kidney and/or Pancreas
UDCA Ursodeoxycholic Acid as Treatment for Polycystic Liver Disease

A few trials for PKD

Study of Lanreotide to Treat Polycystic Kidney Disease
ADPKD low osmolar diet (lots of water)
ADPKD feasibility niacinamide trial

Octreotide

A completed Mayo Octreotide clinical trial from phase I (checking for dose, safety and side effects of once monthly injections of long acting octreotide) has been extended for two additional years to a four year clinical trial of the 42 original participants.

A completed Italian Octreotide clinical trial with Somatostatin has concluded that Octreotide is beneficial for diminishing kidney cysts. In progress is a three year follow up trial at the Mario Negri Institute for Pharmacological Research, Bergamo, Italy.

Pasireotide

The Mayo Clinic Rochester, Minnesota USA is recruiting for Pasireotide (octreotide LAR) trial for individuals with PLD who have never before taken octreotide. Calling all participants who live near the Mayo; one would have to go to the Mayo Clinic once every 28 days for the injections. Pros are receiving medical care and follow up from PLD experts.

Some individuals will receive a placebo. Though participants must travel to the Mayo every 28 days for injections, one has the benefit of PLD experts checking out PLD. All participants willing to travel to the Mayo for monthly injections please contact study coordinators.

Lanreotide

A clinical trial from the Netherlands uses Lanreotide. There is a study in Belgium, and in Italy. We are very hopeful this drug will prove useful for the treatment of PLD Polycystic Liver Disease.

Sirolimus

Sirolimus is a drug given for transplants. The Mayo Clinic in the USA is looking at cystic livers with individuals already taking sirolimus. A paper written by Dr Torres shows that sirolimus decreases liver cyst growth. Rapamune/sirolimus has some very serious side effects. 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, and currently taking it, Rapamune sirolimus might be useful as it also reduces liver cysts.

ADPLD Genetic Study

This study is for individuals with only liver cysts, without any kidney cysts. Without kidney cysts and only liver cysts, it is likely that this is ADPLD, autosomal dominant polycystic liver disease. Your participation would help researchers looking at polycystic liver disease. The researchers for the ADPLD study are Dr. Peter Harris, Dr Torres and Dr. Somlo. This requires a donation of a test tube of your blood. A kit can be mailed to you and you can mail it back in a pre-paid envelope.

PLD Health Questionnaire

Recruitment is underway for participants in a PLD questionnaire from the Mayo Clinic in Rochester, Minnesota.

UDCA Ursodeoxycholic acid

Ursodeoxycholic acid is a bile acid. Take this medicine with or immediately after food. Try to avoid eating foods that are high in calories or cholesterol. Do not take antacid preparations at the same time as this medicine. Some indigestion remedies also prevent ursodeoxycholic acid from working properly.

Experimental evidence with ursodeoxycholic acid (UDCA)suggests three major mechanisms of action:
(1) protection of cholangiocytes against cytotoxicity
(2) stimulation of hepatobiliary secretion.
(3) protection of hepatocytes against bile acid-induced apoptosis, may delay disease progression to severe fibrosis or cirrhosis, and prolong a transplant-free survival.

Its use in a clinical trial for PLD polycystic liver disease is thought to
(1) reduce liver volume in PLD.
(2) inhibit proliferation cholangiocytes. Cholangiocytes are only cells that form liver cysts.
(3) normalization of the intracellular calcium levels in cystic cholangiocytes.

Treatment With UDCA Ursodeoxycholic Acid

(1) A patient developed asymptomatic cholelithiasis during somatostatin therapy, after two months of treatment with ursodeoxycholic Acid the patient was in remission.
(2) Caroli's disease stabilized after treatment with UDCA.
(3) Liver cancers are lessened.
(4) Primary biliary cirrhosis improves with treatment.
(5) In gallbladder disease Ursodeoxycholic Acid is useful as an anti-inflammatory.
(6) Autoimmune pancreatitis has responded to treatment with UDCA.

A few 2015 Articles

J Am Soc Nephrol. 2015 Nov 4. pii: ASN.2015020132.
Food Restriction Ameliorates the Development of Polycystic Kidney Disease.

UDCA Trial Does Not Hold Promise for PLD.

Trial Sclerotherapy Plus Pasireotide

Sclerotherapy Infection

Ther Apher Dial. 2015 Oct 20. doi: 10.1111/1744-9987.12326.
Ursodeoxycholic Acid for Treatment of Enlarged Polycystic Liver.
Ursodeoxycholic Acid UDCA was administered for 1 year at a dose of 300 mg daily to seven PLD patients. Liver volumes were compared among three time points: 1 year before UDCA treatment, at the start of UDCA therapy, and 1 year after the start of therapy. Liver volume decreased significantly to 98?IU/L after 1 year of UDCA therapy.

Hepatol Res. 2015 Jul 20. doi: 10.1111/hepr.12560.
Comparison of volume-reductive therapies for massive polycystic liver disease in autosomal dominant polycystic kidney disease.
28 ADPKD patients who underwent TAE, liver resection or liver transplantation for PLD at a single center, and compared their outcomes. Liver resection is a good first-line therapy in patients that have severe symptoms, cyst involvement in several segments with some spared segments and preserved liver function. Liver transplantation is a preferred first-line therapy in patients with poor liver function or whole-liver involvement. Liver transplantation is also a good rescue therapy following TAE or liver resection.

Mayo Clin Proc. 2015 Aug;90(8):1030-7.
Efficacy of 4 Years of Octreotide Long-Acting Release Therapy in Patients With Severe Polycystic Liver Disease
OctLAR over 4 years in selected patients with symptomatic PLD arrested PLD progression, alleviating symptoms and improving health-related QoL. Discontinuation led to organ regrowth..

J Pediatr Gastroenterol Nutr. 2015 Apr
Feeding soy protein isolate and n-3 PUFA affects polycystic liver disease progression in a PCK rat model of autosomal polycystic kidney disease.
Feeding soy based diet resulted in complications of hepatic steatosis attributable to cysts obstruction of bile duct and hepatic vein..

Rocz Panstw Zakl Hig. 2015;66(1):5-11
Health risk of exposure to Bisphenol A (BPA)
BPA is metabolized in the liver to form bisphenol A glucuronide and mostly in this form is excreted with urine. Due to its phenolic structure BPA has been shown to interact with estrogen receptors. PLD cysts contain estrogen receptors

Ann Endocrinol (Paris). 2013
Bisphenol A: an endocrine and metabolic disruptor.
Bisphenol A (BPA), initially designed, like diethylstilbestrol, as a synthetic estrogen, has been rapidly and widely used for its cross-linking properties in the manufacture of polycarbonate plastics and epoxy resins. Exposure to such environmentally relevant doses of BPA has been shown to affect the liver.

Curr Mol Med. 2012 Jan;12(1):68-82.
The emerging role of endocrine disruptors in pathogenesis of insulin resistance: a concept implicating nonalcoholic fatty liver disease.
Certain endocrine-disrupting chemicals EDCs may be responsible for inducing alterations similar to those encountered in Nonalcoholic fatty liver disease NAFLD either directly through a hepatotoxic effect and/or indirectly by triggering hepatic and systematic insulin resistance IR.

Toxicol Sci. 2015 Oct 26. pii: kfv231.
Inhibition of Human Hepatic Bile Acid Transporters by Tolvaptan and Metabolites: Contributing Factors to Drug-Induced Liver Injury
Based on this date, inhibition of hepatic bile acid transport may be one of the biological mechanisms underlying tolvaptan-associated liver injury in patients with ADPKD.