Oral Galactose in Children With Steroid Resistant Nephrotic Syndrome

NCT01113385 | Completed Results

• 1 other identifier: 4657
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Focal Segmental Glomerulosclerosis; Steroid Resistant Nephrotic Syndrome

Keywords

Nephrotic syndrome; Focal Segmental glomerulosclerosis; FSGS; Minimal change; Steroid resistant; Pediatric; Proteinuria; Galactose; FSPF

Outcome Measures

Primary Outcomes (1)

• Focal Segmental Glomerulosclerosis Permeability Factor (FSPF)

  FSPF is reported in relation to its induction of glomerular albumin permeability (Palb) of isolated glomeruli on a range from 0 to 1, with 0 indicative of normal glomeruli and 1 indicative of injury to the permeability barrier. 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 Palb or decrease in FSPF by \> 0.3 Palb.

  16 weeks

Secondary Outcomes (1)

• Number of Participants Achieving Complete or Partial Remission at 16 Weeks

  16 weeks

Study Arms (1)

Galactose

EXPERIMENTAL

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

Interventions

D-Galactose DRUG

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.

Also known as: Galactose

Galactose

Eligibility Criteria

• Age: 2 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Children's National Research Institute: lead
• National Kidney Foundation, United States: collaborator

Study Sites (1)

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Related Publications (13)

• Fine RN. Recurrence of nephrotic syndrome/focal segmental glomerulosclerosis following renal transplantation in children. Pediatr Nephrol. 2007 Apr;22(4):496-502. doi: 10.1007/s00467-006-0361-6. Epub 2006 Dec 21.

  PMID: 17186280 BACKGROUND

• 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. doi: 10.1007/s004670050555.

  PMID: 10100283 BACKGROUND

• Tryggvason K, Patrakka J, Wartiovaara J. Hereditary proteinuria syndromes and mechanisms of proteinuria. N Engl J Med. 2006 Mar 30;354(13):1387-401. doi: 10.1056/NEJMra052131. No abstract available.

  PMID: 16571882 BACKGROUND

• 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.

  PMID: 15384010 BACKGROUND

• Burdmann EA, Andoh TF, Yu L, Bennett WM. Cyclosporine nephrotoxicity. Semin Nephrol. 2003 Sep;23(5):465-76. doi: 10.1016/s0270-9295(03)00090-1.

  PMID: 13680536 BACKGROUND

• 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. doi: 10.1016/j.trsl.2008.04.001. Epub 2008 May 2.

  PMID: 18514139 BACKGROUND

• 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. doi: 10.1056/NEJM199604043341402.

  PMID: 8596570 BACKGROUND

• 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.

  PMID: 1278655 BACKGROUND

• 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. doi: 10.1056/NEJM200107053450104. No abstract available.

  PMID: 11439944 BACKGROUND

• 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. doi: 10.1007/s10552-005-0455-7.

  PMID: 16489535 BACKGROUND

• 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. doi: 10.1097/00008469-200502000-00003.

  PMID: 15677891 BACKGROUND

• 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.

  PMID: 951142 BACKGROUND

• De Smet E, Rioux JP, Ammann H, Deziel C, Querin S. FSGS permeability factor-associated nephrotic syndrome: remission after oral galactose therapy. Nephrol Dial Transplant. 2009 Sep;24(9):2938-40. doi: 10.1093/ndt/gfp278. Epub 2009 Jun 9.

  PMID: 19509024 BACKGROUND

MeSH Terms

Conditions

Glomerulosclerosis, Focal Segmental; Nephrotic Syndrome; Proteinuria

Interventions

Galactose

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Nephrosis; Urination Disorders; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Hexoses; Monosaccharides; Sugars; Carbohydrates

Results Point of Contact

• Title: Asha Moudgil MD, Professor of Pediatrics
• Organization: Children's National

amoudgil@childrensnational.org

202-476-5058

Study Officials

• Asha Moudgil, MD

  Children's National Research Institute

  PRINCIPAL INVESTIGATOR

• Kristen Sgambat, MS, RD

  Children's National Research Institute

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics

Study Record Dates

• First Submitted: April 28, 2010
• First Posted: April 29, 2010
• Study Start: October 1, 2009
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2013
• Last Updated: September 15, 2014
• Results First Posted: September 15, 2014

Record last verified: 2014-09

Locations

US (1)