Oral Galactose in Children With Steroid Resistant Nephrotic Syndrome - Full Text View

Purpose

Focal Segmental Glomerulosclerosis (FSGS) is a devastating kidney disease which is difficult to treat and carries a poor prognosis, with 50% of affected children progressing to end stage renal disease (ESRD). The purpose of this study is to investigate oral galactose as a benign treatment for FSGS in children. The investigators hypothesize that galactose, a simple milk sugar thought to bind to the protein factor (FSPF) that causes FSGS thereby inactivating it and stopping it from damaging the kidney, resulting in a reduction in glomerular permeability to albumin and decrease in proteinuria in children with nephrotic syndrome secondary to FSGS.

Condition	Intervention
Focal Segmental Glomerulosclerosis Steroid Resistant Nephrotic Syndrome	Drug: D-Galactose

Study Type:	Interventional
Study Design:	Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Effect of Oral Galactose on the Level of Focal Sclerosis Permeability Factor and Proteinuria in Children With Steroid Resistant Nephrotic Syndrome: A Pilot Study

Resource links provided by NLM:

MedlinePlus related topics: Urine and Urination

U.S. FDA Resources

Further study details as provided by Children's Research Institute:

Primary Outcome Measures:

FSPF [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
Results will be considered clinically significant if the following criteria is met in response to oral galactose therapy at week 16: Reduction in FSPF to <0.5 or decrease in FSPF by > 0.3

Secondary Outcome Measures:

Urine protein:creatinine ratio [ Time Frame: 28 weeks ] [ Designated as safety issue: No ]
Results will be considered clinically significant if the following criteria is met in response to oral galactose therapy at week 16 and persists at 12 weeks after discontinuation of galactose: Decrease in first morning urine protein: creatinine ratio by 50%
Serum albumin [ Time Frame: 28 weeks ] [ Designated as safety issue: No ]
Results will be considered clinically significant if the following criteria is met in response to oral galactose therapy at week 16 persists at 12 weeks after discontinuation of galactose: Increase in serum albumin by >1gm/dl

Enrollment:	7
Study Start Date:	October 2009
Study Completion Date:	March 2013
Primary Completion Date:	March 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Galactose Oral galactose will be given at a dose of 0.2gm/kg/dose twice a day (BID) to a maximum of 15 gm BID for a period of 16 weeks.	Drug: D-Galactose Oral galactose will be initiated at a dose of 0.2gm/kg/dose twice daily to a maximum of 15 gm BID for a period of 4 months. The prescribed dose of D-galactose powder will be dispensed to subjects in packets, mixed with 4 ounces of water, and consumed orally. Other Names: D-galactose Galactose

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Eligibility

Ages Eligible for Study:	2 Years to 21 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

2-21 years old
Biopsy proven FSGS or minimal change with steroid resistance
Presence of FSPF (defined as permeability activity >0.5)
Presence of nephrotic range proteinuria (urine protein: creatinine ratio >2) at the time of enrollment.
Persistent nephrotic range proteinuria despite being on stable immunosuppressive medications (cyclosporine, tacrolimus or mycophenolate mofetil) for at least 12 weeks and/or persistent nephrotic range proteinuria despite being on stable dose of angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) for 12 weeks.
Stable serum creatinine (change of less than 0.3 mg/dl) in the prior 3 months.
Schwartz estimated (e) glomerular filtration rate (GFR) >60ml/min/1.73m2

Exclusion Criteria:

Secondary FSGS
Onset of nephrotic syndrome in infancy.
Presence of acute renal failure (as defined by acute kidney injury criteria) at the time of enrollment. These children can be enrolled 1 month after resolution of acute renal failure (ARF).
Decreasing renal function (persistent increase in serum creatinine of greater than 0.3 mg/dl over baseline in the prior 3 months).
Use of another investigational drug
Pregnant or unable to comply with contraceptive measures in females of child bearing age
eGFR < 60 ml/min per 1.73 m2
Children with Galactosemia
Children with type 1 or 2 diabetes

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01113385

Locations

United States, District of Columbia
Children's National Medical Center
Washington DC, District of Columbia, United States, 20010

Sponsors and Collaborators

Children's Research Institute

National Kidney Foundation

Investigators

Principal Investigator:	Asha Moudgil, MD	Children's Research Institute
Study Director:	Kristen Sgambat, MS, RD	Children's Research Institute

More Information

Publications:

Fine RN. Recurrence of nephrotic syndrome/focal segmental glomerulosclerosis following renal transplantation in children. Pediatr Nephrol. 2007 Apr;22(4):496-502. Epub 2006 Dec 21. Review.

Srivastava T, Simon SD, Alon US. High incidence of focal segmental glomerulosclerosis in nephrotic syndrome of childhood. Pediatr Nephrol. 1999 Jan;13(1):13-8.

Tryggvason K, Patrakka J, Wartiovaara J. Hereditary proteinuria syndromes and mechanisms of proteinuria. N Engl J Med. 2006 Mar 30;354(13):1387-401. Review. No abstract available.

Trachtman H, Greenbaum LA, McCarthy ET, Sharma M, Gauthier BG, Frank R, Warady B, Savin VJ. Glomerular permeability activity: prevalence and prognostic value in pediatric patients with idiopathic nephrotic syndrome. Am J Kidney Dis. 2004 Oct;44(4):604-10.

Burdmann EA, Andoh TF, Yu L, Bennett WM. Cyclosporine nephrotoxicity. Semin Nephrol. 2003 Sep;23(5):465-76. Review.

Savin VJ, McCarthy ET, Sharma R, Charba D, Sharma M. Galactose binds to focal segmental glomerulosclerosis permeability factor and inhibits its activity. Transl Res. 2008 Jun;151(6):288-92. Epub 2008 May 2.

Savin VJ, Sharma R, Sharma M, McCarthy ET, Swan SK, Ellis E, Lovell H, Warady B, Gunwar S, Chonko AM, Artero M, Vincenti F. Circulating factor associated with increased glomerular permeability to albumin in recurrent focal segmental glomerulosclerosis. N Engl J Med. 1996 Apr 4;334(14):878-83.

Shreeve WW, Shoop JD, Ott DG, McInteer BB. Test for alcoholic cirrhosis by conversion of [14C]- or [13C]galactose to expired CO2. Gastroenterology. 1976 Jul;71(1):98-101.

Frustaci A, Chimenti C, Ricci R, Natale L, Russo MA, Pieroni M, Eng CM, Desnick RJ. Improvement in cardiac function in the cardiac variant of Fabry's disease with galactose-infusion therapy. N Engl J Med. 2001 Jul 5;345(1):25-32. No abstract available.

Genkinger JM, Hunter DJ, Spiegelman D, Anderson KE, Beeson WL, Buring JE, Colditz GA, Fraser GE, Freudenheim JL, Goldbohm RA, Hankinson SE, Koenig KL, Larsson SC, Leitzmann M, McCullough ML, Miller AB, Rodriguez C, Rohan TE, Ross JA, Schatzkin A, Schouten LJ, Smit E, Willett WC, Wolk A, Zeleniuch-Jacquotte A, Zhang SM, Smith-Warner SA. A pooled analysis of 12 cohort studies of dietary fat, cholesterol and egg intake and ovarian cancer. Cancer Causes Control. 2006 Apr;17(3):273-85.

Qin LQ, Xu JY, Wang PY, Hashi A, Hoshi K, Sato A. Milk/dairy products consumption, galactose metabolism and ovarian cancer: meta-analysis of epidemiological studies. Eur J Cancer Prev. 2005 Feb;14(1):13-9.

Schwartz GJ, Haycock GB, Edelmann CM Jr, Spitzer A. A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics. 1976 Aug;58(2):259-63.

De Smet E, Rioux JP, Ammann H, Déziel C, Quérin S. FSGS permeability factor-associated nephrotic syndrome: remission after oral galactose therapy. Nephrol Dial Transplant. 2009 Sep;24(9):2938-40. Epub 2009 Jun 9.

Responsible Party:	Asha Moudgil, Professor of Pediatrics, Children's Research Institute
ClinicalTrials.gov Identifier:	NCT01113385 History of Changes
Other Study ID Numbers:	4657
Study First Received:	April 28, 2010
Last Updated:	March 7, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Children's Research Institute:

Nephrotic syndrome
Focal Segmental glomerulosclerosis
FSGS
Minimal change
Steroid resistant

Pediatric
Proteinuria
Galactose
FSPF

Additional relevant MeSH terms:

Glomerulosclerosis, Focal Segmental
Nephrotic Syndrome
Proteinuria
Glomerulonephritis
Nephritis
Kidney Diseases

Urologic Diseases
Nephrosis
Urination Disorders
Urological Manifestations
Signs and Symptoms

ClinicalTrials.gov processed this record on May 19, 2013