title: Somatostatin analog therapy for severe polycystic liver disease: results after 2 years.
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 TLV after 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.
  
  
  CONCLUSIONS
  Over 2 years, OctLAR significantly reduced the rate of increase in TLV and possibly the rate of increase in TKV.
authors: Department of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA. hogan.marie@mayo.edu
authors: Marie C
authors: MC
authors: Hogan
authors: Tetyana V
authors: TV
authors: Masyuk
authors: Linda
authors: L
authors: Page
authors: David R
authors: DR
authors: Holmes
authors: Xujian
authors: X
authors: Li
authors: Eric J
authors: EJ
authors: Bergstralh
authors: Maria V
authors: MV
authors: Irazabal
authors: Bohyun
authors: B
authors: Kim
authors: Bernard F
authors: BF
authors: King
authors: James F
authors: JF
authors: Glockner
authors: Nicholas F
authors: NF
authors: Larusso
authors: Vicente E
authors: VE
authors: Torres
mesh_terms: D000293:Adolescent; D018592:Cross-Over Studies; D003560:Cysts / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006728:Hormones / Q000627:therapeutic use*; D006801:Humans; D007674:Kidney Diseases / Q000209:etiology* / Q000473:pathology; D008107:Liver Diseases / Q000150:complications / Q000188:drug therapy*; D008279:Magnetic Resonance Imaging; D008297:Male; D011379:Prognosis; D011788:Quality of Life; D012307:Risk Factors; D013004:Somatostatin / Q000031:analogs & derivatives / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D006728:Hormones; D013004:Somatostatin