Symptoms and General Pathology

All Conditions

Neoplasms

Nutritional and Metabolic Diseases

Syndrome

Head and Neck Neoplasms

Hypophosphatemia

Refeeding Syndrome

Hypokalemia

Potassium Deficiency

Malnutrition

Nutrition Disorders

Low sodium diet

Jens R. Andersen, MD, lektor

The study is based on a master thesis which showed that 72% of patients with head and neck cancer admitted to a Danish hospital (Rigshospitalet, Copenhagen) developed refeeding syndrome after admission.

Refeeding syndrome is characterized by a decrease in plasma phosphate levels, which develops after the reintroduction of an adequate food intake after a longer period of starvation or semi-starvation. This normally happens within 7 days after reintroduction of food.

The aim of this study is to minimize the incidence of refeeding syndrome in this group of patients by reintroducing food slowly and by providing a diet low in sodium and high in slowly absorbed carbohydrates as a prevention diet (i.e. given before a potential decrease in plasma phosphate levels appear). Both patients that eat normally, patients with eating tubes and patients with central vein catheters are included in the study, but the data will be evaluated both together and separately.

A large weight loss as a result of a longer period (\>30 days) of starvation or semi-starvation will result in a metabolic adaptation to the decreased food intake. To prevent the degradation of muscle mass into gluco- and ketogenic amino acids to be used for energy production, a shift from gluconeogenesis to lipolysis occurs. Lipids therefore become the primary energy fuel, and the body adapts to use ketone bodies instead of glucose. The reduction in glucose metabolism results in a decreased need for amino acids for use in gluconeogenesis. This means that less amino acids are needed for gluconeogenesis and therefore important muscle mass is preserved. At the same time as the lipid stores are degraded, an intracellular depletion of phosphate, potassium and magnesium occurs. The serum levels of these electrolytes stay within the normal range as long as the body is in the adaptive starvation state. A too quick reintroduction of food to the body will result in a major glucose-induced increase in insulin secretion that will stimulate the transport of glucose, phosphate, potassium and magnesium from plasma into the cells. Because the extracellular blood volume is much smaller than the intracellular, an influx of these electrolytes to the intracellular space will result in a quick and large decrease in the plasma levels. Likewise, an influx of glucose means that it again can enter the glucolysis, and the need for phosphate and the co-factor thiamine, for the production of ATP, will increase. The increased production of adenosine triphosphate (ATP) will activate membrane pumps and reestablish the membrane potential. This means that sodium will be transported from the large intracellular space to the small extracellular, with subsequent fluid retention and edema formation.

Therefore a slowly introduced diet low in sodium and high in slowly absorbed carbohydrates might prevent the development of refeeding syndrome.

The Effect of a Diet Based on Low Sodium and Slowly Absorbed Carbohydrates on the Incidence of Refeeding Syndrome in Patients With Head and Neck Cancer

The Prevention of Refeeding Syndrome by a Diet Regime in Patient With Head and Neck Cancer

Measured by changes in plasma cobalamin levels/vitamin B12 levels (pmol/L), plasma iron levels (μmol/L), plasma ferritin levels (μg/L), mean cell volume (MCV) (fL), plasma albumin levels (μmol/L), plasma alanine aminotransferase levels (ALAT) (U/L), plasma coagulation factors II, VII, X levels (INR), plasma c-reactive protein levels (nmol/L), hemoglobin levels (Hgb) (mmol/L), plasma sodium levels (mmol/L), plasma potassium levels (mmol/L), plasma creatinine levels (μmol/L), plasma carbamide levels (mmol/L), plasma folate levels (nmol/L), plasma zink levels (μmol/L), plasma magnesium levels (mmol/L) and plasma selenium levels (μg/L).

Measured by a decrease in plasma phosphate levels.

Measured by infection events recorded in the medical journal.

Measured by number of days in the hospital

Measured by number of days in the intensive-care unit

Measured by thrombosis events and other complications recorded in the medical journal

University of Copenhagen

Professor

Musculoskeletal Diseases

Rare Diseases

Osteomalacia

Rickets

Bone Diseases

Bone Diseases, Metabolic

Metabolic Diseases

Calcium Metabolism Disorders

Vitamin D Deficiency

Avitaminosis

Deficiency Diseases

Oncogenic Osteomalacia

This study will use a procedure called selective venous catheterization in patients with tumor-induced osteomalacia (TIO) or oncogenic osteomalacia (OOM) to try to locate very small tumors that produce proteins called phosphatonins. Too much phosphatonin in the blood causes the kidneys to allow large amounts of phosphorus to be excreted in the urine, leading to low blood levels of phosphorus and, in turn, to osteomalacia (a condition of soft bones). Osteomalacia can cause bone fractures requiring many surgical procedures that can leave patients in pain. Patients may also feel weak and can lose height from massive bone loss. Selective venous catheterization is a way to measure the amount of phosphatonin in the blood and may be used as a way to locate phosphatonin-producing tumors that cannot be found using standard imaging techniques.

Patients with TIO or OOM are screened under NIDR Protocol 01-D-0184 with a medical history, review of medical records and routine physical examination. Other procedures may include blood tests, urine tests, and imaging tests, such as x-rays, bone densitometry, bone scan, computed tomography (CT) and magnetic resonance imaging (MRI). This study will include mostly patients whose tumors were not able to be located through imaging procedures, but also a few patients whose tumors were located.

All participants, regardless of whether or not their tumor was located, undergo selective venous catheterization. For this procedure, a radiologist inserts a catheter (thin flexible tube) into the body and uses fluoroscopy (a type of x-ray) to guide the tip of the catheter to different places in the body to collect small amounts of blood from the different areas. After the procedure, the patient lies flat for 2 hours and avoids moving his or her leg on the side where the catheter was placed.

The blood is analyzed to measure the amount phosphatonin is in each sample, and the amounts are compared to the average amount of phosphatonin in the general blood circulation. If a higher level of phosphatonin is found in one area and the location of the tumor is unknown, the patient undergoes imaging in that area. If a tumor is found and it is in an area where it can be removed surgically, the patient is given the option to have the surgery. If the tumor is not found by imaging done after the first catheterization procedure, the patient has the option to have a second catheterization, taking samples of blood only from the area where the phosphatonin was found to be the highest during the sampling procedure.

Phosphaturic mesenchymal tumors elaborate phosphate lowering factors (phosphatonins) which lead to tumor induced osteomalacia/osteogenic osteomalacia (TIO/OOM). Patients with TIO/OOM suffer years of significant morbidity and debilitation unless their tumors, which are notoriously difficult to locate, are removed.

Selective venous catheterization has been used to localize hormonally active neoplasms by demonstrating a gradient in the concentration of the hormone of interest between the vessel immediately draining the tumor site and the peripheral circulation. The primary objective of this protocol is to evaluate the utility of combining selective venous catheterization with biochemical assays that identify phosphatonins in the serum as a way to identify phosphatonin gradients and thereby localize phosphaturic tumors.

Our study population will consist of TIO/OOM patients with non-localized phosphaturic tumors as well as five patients whose lesions have been identified with some certainty by conventional imaging techniques. These individuals will undergo selective venous catheterization during which blood samples will be obtained and processed for the presence of phosphatonins. The primary endpoint will be met if a gradient indicating a possible tumor is found, focused clinical imaging in the appropriate anatomical sub-region identifies a lesion, and the lesion is confirmed to be a phosphaturic mesenchymal tumor upon surgical removal.

Catheterization to Locate Mesenchymal Tumors in Patients With Tumor-Induced Osteomalacia or Oncogenic Osteomalacia

Selective Venous Catheterization for the Localization of Phosphaturic Mesenchymal Tumors

National Institute of Dental and Craniofacial Research (NIDCR)

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma

Carcinoma, Renal Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Phosphorus Metabolism Disorders

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Sorafenib

Protein Kinase Inhibitors

Enzyme Inhibitors

Sorafenib will be administered at 400mg BID for a 28 day cycle.

Sorafenib (Nexavar, BAY43-9006)

Bayer Study Director

The purpose of this study is to:

1. To elucidate the mechanism involved in the sorafenib-induced hypophosphatemia and possible early effect of hypophosphatemia on bone mineral density
2. A secondary objective to assess the effect sorafenib treatment on evaluate left ventricular function (LVEF) and Beta-type natriuretic peptide in plasma.

Mechanistic Evaluation on Sorafenib Induced Hypophosphatemia.

Mechanistic Evaluations on Sorafenib Induced Hypophosphatemia in Patients With Advanced Renal Cell Carcinoma

Bayer

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
The Effect of a Diet Based on Low Sodium and Slowly Absorbed Carbohydrates on the Incidence of Refeeding Syndrome in Patients With Head and Neck Cancer	NCT01845922	Refeeding Syndr...	Low sodium diet	18 Years -	University of Copenhagen
Catheterization to Locate Mesenchymal Tumors in Patients With Tumor-Induced Osteomalacia or Oncogenic Osteomalacia	NCT00099762	Osteomalacia Neoplasms		8 Years - 100 Years	National Institutes of Health Clinical Center (CC)
Mechanistic Evaluation on Sorafenib Induced Hypophosphatemia.	NCT00622479	Carcinoma, Rena...	Sorafenib (Nexa...	18 Years -	Bayer

Spots Global Cancer Trial Database for hypophosphatemia