title: Effect of longacting somatostatin analogue on kidney and cyst growth in autosomal dominant polycystic kidney disease (ALADIN): a randomised, placebo-controlled, multicentre trial.
abstract: BACKGROUND
  Autosomal dominant polycystic kidney disease slowly progresses to end-stage renal disease and has no effective therapy. A pilot study suggested that the somatostatin analogue octreotide longacting release (LAR) could be nephroprotective in this context. We aimed to assess the effect of 3 years of octreotide-LAR treatment on kidney and cyst growth and renal function decline in participants with this disorder.
  
  
  METHODS
  We did an academic, multicentre, randomised, single-blind, placebo-controlled, parallel-group trial in five hospitals in Italy. Adult (>18 years) patients with estimated glomerular filtration rate (GFR) of 40 mL/min per 1·73 m(2) or higher were randomly assigned (central allocation by phone with a computerised list, 1:1 ratio, stratified by centre, block size four and eight) to 3 year treatment with two 20 mg intramuscular injections of octreotide-LAR (n=40) or 0·9% sodium chloride solution (n=39) every 28 days. Study physicians and nurses were aware of the allocated group; participants and outcome assessors were masked to allocation. The primary endpoint was change in total kidney volume (TKV), measured by MRI, at 1 year and 3 year follow-up. Analyses were by modified intention to treat. This study is registered with ClinicalTrials.gov, NCT00309283.
  
  
  RESULTS
  Recruitment was between April 27, 2006, and May 12, 2008. 38 patients in the octreotide-LAR group and 37 patients in the placebo group had evaluable MRI scans at 1 year follow-up, at this timepoint, mean TKV increased significantly less in the octreotide-LAR group (46·2 mL, SE 18·2) compared with the placebo group (143·7 mL, 26·0; p=0·032). 35 patients in each group had evaluable MRI scans at 3 year follow-up, at this timepoint, mean TKV increase in the octreotide-LAR group (220·1 mL, 49·1) was numerically smaller than in the placebo group (454·3 mL, 80·8), but the difference was not significant (p=0·25). 37 (92·5%) participants in the octreotide-LAR group and 32 (82·1%) in the placebo group had at least one adverse event (p=0·16). Participants with serious adverse events were similarly distributed in the two treatment groups. However, four cases of cholelithiasis or acute cholecystitis occurred in the octreotide-LAR group and were probably treatment-related.
  
  
  CONCLUSIONS
  These findings provide the background for large randomised controlled trials to test the protective effect of somatostatin analogues against renal function loss and progression to end-stage kidney disease.
  
  
  BACKGROUND
  Polycystic Kidney Disease Foundation.
authors: IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Clinical Research Center for Rare Diseases, Aldo e Cele Daccò, Bergamo, Italy.
authors: Anna
authors: A
authors: Caroli
authors: Norberto
authors: N
authors: Perico
authors: Annalisa
authors: A
authors: Perna
authors: Luca
authors: L
authors: Antiga
authors: Paolo
authors: P
authors: Brambilla
authors: Antonio
authors: A
authors: Pisani
authors: Bianca
authors: B
authors: Visciano
authors: Massimo
authors: M
authors: Imbriaco
authors: Piergiorgio
authors: P
authors: Messa
authors: Roberta
authors: R
authors: Cerutti
authors: Mauro
authors: M
authors: Dugo
authors: Luca
authors: L
authors: Cancian
authors: Erasmo
authors: E
authors: Buongiorno
authors: Antonio
authors: A
authors: De Pascalis
authors: Flavio
authors: F
authors: Gaspari
authors: Fabiola
authors: F
authors: Carrara
authors: Nadia
authors: N
authors: Rubis
authors: Silvia
authors: S
authors: Prandini
authors: Andrea
authors: A
authors: Remuzzi
authors: Giuseppe
authors: G
authors: Remuzzi
authors: Piero
authors: P
authors: Ruggenenti
mesh_terms: D000328:Adult; D041881:Cholecystitis, Acute / Q000139:chemically induced; D002769:Cholelithiasis / Q000139:chemically induced; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005765:Gastrointestinal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007558:Italy; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000517:prevention & control*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000009:adverse effects / Q000627:therapeutic use*; D009929:Organ Size / Q000187:drug effects; D016891:Polycystic Kidney, Autosomal Dominant / Q000188:drug therapy* / Q000473:pathology; D013004:Somatostatin / Q000031:analogs & derivatives*; D016896:Treatment Outcome
chemical_list: D005765:Gastrointestinal Agents; D013004:Somatostatin; D015282:Octreotide