Somatostatin analog therapy for severe polycystic liver disease: Results after 2 years

Marie C Hogan, Tetyana V. Masyuk, Linda Page, David R. Holmes III, Xujian Li, Eric J. Bergstralh, Maria Irazabal Mira, Bohyun Kim, Bernard Francis King, James Glockner, Nicholas F La Russo, Vicente Torres

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Abstract

Background. We showed in a randomized double-blinded placebo-controlled clinical trial that octreotide long-acting repeatable depot.® (OctLAR®) for 12 months reduces kidney and liver growth in autosomal dominant polycystic kidney patients with severe polycystic liver disease (PLD) and liver growth in patients with severe isolated PLD. We have now completed an open-label extension for one additional year to assess safety and clinical benefits of continued use of OctLAR for 2 years (O→O) and examined drug effect in the placebo group who crossed over to OctLAR in Year 2 (P→O). Methods. The primary end point was change in total liver volume (TLV) measured by magnetic resonance imaging (MRI); secondary end points were changes in total kidney volume (TKV) measured by MRI, glomerular filtration rate (GFR), quality of life (QOL), safety, vital signs and laboratory parameters. Results. Forty-one of 42 patients received OctLAR (n = 28) or placebo (n = 14) in Year 1 and received OctLAR in Year 2 (maximum dose 40 mg). Patients originally randomized to placebo (P→O) showed substantial reduction in TLVafter treatment with OctLAR in Year 2 (δ%-7.66 ± 9.69%, P = 0.011). The initial reduction of TLV in the OctLAR group (O→O) was maintained for 2 years (δ%-5.96 ± 8.90%), although did not change significantly during Year 2 (δ%-0.77 ± 6.82%). OctLAR inhibited renal enlargement during Year 1 (δ% +0.42 ± 7.61%) in the (O→O) group and during Year 2 (δ%-0.41 ± 9.45%) in the (P→O) group, but not throughout Year 2 (δ% +6.49 ± 7.08%) in the (O→O) group. Using pooled analyses of all individuals who received OctLAR for 12 months, i.e. in Year 1 for O→O patients and Year 2 for P→O patients, average reduction in TLV was-6.08 ± 7.58% (P = 0.001) compared to net growth of 0.9 ± 8.35% in the original placebo group. OctLAR-treated individuals continued to experience improvements in QOL in Year 2, although overall physical and mental improvements were not significant during Year 2 compared to Year 1. Changes in GFR were similar in both groups. Conclusion. Over 2 years, OctLAR significantly reduced the rate of increase in TLV and possibly the rate of increase in TKV.

Original languageEnglish (US)
Pages (from-to)3532-3539
Number of pages8
JournalNephrology Dialysis Transplantation
Volume27
Issue number9
DOIs
StatePublished - Sep 2012

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Somatostatin
Placebos
Liver
Kidney
Glomerular Filtration Rate
Therapeutics
Growth
Quality of Life
Magnetic Resonance Imaging
Safety
Autosomal Dominant Polycystic Kidney
Placebo Effect
Octreotide
Vital Signs
Controlled Clinical Trials
Polycystic liver disease
Pharmaceutical Preparations

Keywords

  • chronic kidney disease
  • kidney volume
  • liver cyst
  • polycystic kidney disease
  • somatostatin analogs

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

Somatostatin analog therapy for severe polycystic liver disease : Results after 2 years. / Hogan, Marie C; Masyuk, Tetyana V.; Page, Linda; Holmes III, David R.; Li, Xujian; Bergstralh, Eric J.; Irazabal Mira, Maria; Kim, Bohyun; King, Bernard Francis; Glockner, James; La Russo, Nicholas F; Torres, Vicente.

In: Nephrology Dialysis Transplantation, Vol. 27, No. 9, 09.2012, p. 3532-3539.

Research output: Contribution to journalArticle

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abstract = "Background. We showed in a randomized double-blinded placebo-controlled clinical trial that octreotide long-acting repeatable depot.{\circledR} (OctLAR{\circledR}) for 12 months reduces kidney and liver growth in autosomal dominant polycystic kidney patients with severe polycystic liver disease (PLD) and liver growth in patients with severe isolated PLD. We have now completed an open-label extension for one additional year to assess safety and clinical benefits of continued use of OctLAR for 2 years (O→O) and examined drug effect in the placebo group who crossed over to OctLAR in Year 2 (P→O). Methods. The primary end point was change in total liver volume (TLV) measured by magnetic resonance imaging (MRI); secondary end points were changes in total kidney volume (TKV) measured by MRI, glomerular filtration rate (GFR), quality of life (QOL), safety, vital signs and laboratory parameters. Results. Forty-one of 42 patients received OctLAR (n = 28) or placebo (n = 14) in Year 1 and received OctLAR in Year 2 (maximum dose 40 mg). Patients originally randomized to placebo (P→O) showed substantial reduction in TLVafter treatment with OctLAR in Year 2 (δ{\%}-7.66 ± 9.69{\%}, P = 0.011). The initial reduction of TLV in the OctLAR group (O→O) was maintained for 2 years (δ{\%}-5.96 ± 8.90{\%}), although did not change significantly during Year 2 (δ{\%}-0.77 ± 6.82{\%}). OctLAR inhibited renal enlargement during Year 1 (δ{\%} +0.42 ± 7.61{\%}) in the (O→O) group and during Year 2 (δ{\%}-0.41 ± 9.45{\%}) in the (P→O) group, but not throughout Year 2 (δ{\%} +6.49 ± 7.08{\%}) in the (O→O) group. Using pooled analyses of all individuals who received OctLAR for 12 months, i.e. in Year 1 for O→O patients and Year 2 for P→O patients, average reduction in TLV was-6.08 ± 7.58{\%} (P = 0.001) compared to net growth of 0.9 ± 8.35{\%} in the original placebo group. OctLAR-treated individuals continued to experience improvements in QOL in Year 2, although overall physical and mental improvements were not significant during Year 2 compared to Year 1. Changes in GFR were similar in both groups. Conclusion. Over 2 years, OctLAR significantly reduced the rate of increase in TLV and possibly the rate of increase in TKV.",
keywords = "chronic kidney disease, kidney volume, liver cyst, polycystic kidney disease, somatostatin analogs",
author = "Hogan, {Marie C} and Masyuk, {Tetyana V.} and Linda Page and {Holmes III}, {David R.} and Xujian Li and Bergstralh, {Eric J.} and {Irazabal Mira}, Maria and Bohyun Kim and King, {Bernard Francis} and James Glockner and {La Russo}, {Nicholas F} and Vicente Torres",
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T1 - Somatostatin analog therapy for severe polycystic liver disease

T2 - Results after 2 years

AU - Hogan, Marie C

AU - Masyuk, Tetyana V.

AU - Page, Linda

AU - Holmes III, David R.

AU - Li, Xujian

AU - Bergstralh, Eric J.

AU - Irazabal Mira, Maria

AU - Kim, Bohyun

AU - King, Bernard Francis

AU - Glockner, James

AU - La Russo, Nicholas F

AU - Torres, Vicente

PY - 2012/9

Y1 - 2012/9

N2 - Background. We showed in a randomized double-blinded placebo-controlled clinical trial that octreotide long-acting repeatable depot.® (OctLAR®) for 12 months reduces kidney and liver growth in autosomal dominant polycystic kidney patients with severe polycystic liver disease (PLD) and liver growth in patients with severe isolated PLD. We have now completed an open-label extension for one additional year to assess safety and clinical benefits of continued use of OctLAR for 2 years (O→O) and examined drug effect in the placebo group who crossed over to OctLAR in Year 2 (P→O). Methods. The primary end point was change in total liver volume (TLV) measured by magnetic resonance imaging (MRI); secondary end points were changes in total kidney volume (TKV) measured by MRI, glomerular filtration rate (GFR), quality of life (QOL), safety, vital signs and laboratory parameters. Results. Forty-one of 42 patients received OctLAR (n = 28) or placebo (n = 14) in Year 1 and received OctLAR in Year 2 (maximum dose 40 mg). Patients originally randomized to placebo (P→O) showed substantial reduction in TLVafter treatment with OctLAR in Year 2 (δ%-7.66 ± 9.69%, P = 0.011). The initial reduction of TLV in the OctLAR group (O→O) was maintained for 2 years (δ%-5.96 ± 8.90%), although did not change significantly during Year 2 (δ%-0.77 ± 6.82%). OctLAR inhibited renal enlargement during Year 1 (δ% +0.42 ± 7.61%) in the (O→O) group and during Year 2 (δ%-0.41 ± 9.45%) in the (P→O) group, but not throughout Year 2 (δ% +6.49 ± 7.08%) in the (O→O) group. Using pooled analyses of all individuals who received OctLAR for 12 months, i.e. in Year 1 for O→O patients and Year 2 for P→O patients, average reduction in TLV was-6.08 ± 7.58% (P = 0.001) compared to net growth of 0.9 ± 8.35% in the original placebo group. OctLAR-treated individuals continued to experience improvements in QOL in Year 2, although overall physical and mental improvements were not significant during Year 2 compared to Year 1. Changes in GFR were similar in both groups. Conclusion. Over 2 years, OctLAR significantly reduced the rate of increase in TLV and possibly the rate of increase in TKV.

AB - Background. We showed in a randomized double-blinded placebo-controlled clinical trial that octreotide long-acting repeatable depot.® (OctLAR®) for 12 months reduces kidney and liver growth in autosomal dominant polycystic kidney patients with severe polycystic liver disease (PLD) and liver growth in patients with severe isolated PLD. We have now completed an open-label extension for one additional year to assess safety and clinical benefits of continued use of OctLAR for 2 years (O→O) and examined drug effect in the placebo group who crossed over to OctLAR in Year 2 (P→O). Methods. The primary end point was change in total liver volume (TLV) measured by magnetic resonance imaging (MRI); secondary end points were changes in total kidney volume (TKV) measured by MRI, glomerular filtration rate (GFR), quality of life (QOL), safety, vital signs and laboratory parameters. Results. Forty-one of 42 patients received OctLAR (n = 28) or placebo (n = 14) in Year 1 and received OctLAR in Year 2 (maximum dose 40 mg). Patients originally randomized to placebo (P→O) showed substantial reduction in TLVafter treatment with OctLAR in Year 2 (δ%-7.66 ± 9.69%, P = 0.011). The initial reduction of TLV in the OctLAR group (O→O) was maintained for 2 years (δ%-5.96 ± 8.90%), although did not change significantly during Year 2 (δ%-0.77 ± 6.82%). OctLAR inhibited renal enlargement during Year 1 (δ% +0.42 ± 7.61%) in the (O→O) group and during Year 2 (δ%-0.41 ± 9.45%) in the (P→O) group, but not throughout Year 2 (δ% +6.49 ± 7.08%) in the (O→O) group. Using pooled analyses of all individuals who received OctLAR for 12 months, i.e. in Year 1 for O→O patients and Year 2 for P→O patients, average reduction in TLV was-6.08 ± 7.58% (P = 0.001) compared to net growth of 0.9 ± 8.35% in the original placebo group. OctLAR-treated individuals continued to experience improvements in QOL in Year 2, although overall physical and mental improvements were not significant during Year 2 compared to Year 1. Changes in GFR were similar in both groups. Conclusion. Over 2 years, OctLAR significantly reduced the rate of increase in TLV and possibly the rate of increase in TKV.

KW - chronic kidney disease

KW - kidney volume

KW - liver cyst

KW - polycystic kidney disease

KW - somatostatin analogs

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DO - 10.1093/ndt/gfs152

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