title: Metformin and sitAgliptin in patients with impAired glucose tolerance and a recent TIA or minor ischemic Stroke (MAAS): study protocol for a randomized controlled trial.
abstract: BACKGROUND
  Impaired glucose tolerance is present in one third of patients with a TIA or ischemic stroke and is associated with a two-fold risk of recurrent stroke. Metformin improves glucose tolerance, but often leads to side effects. The aim of this study is to explore the feasibility, safety, and effects on glucose metabolism of metformin and sitagliptin in patients with TIA or minor ischemic stroke and impaired glucose tolerance. We will also assess whether a slow increase in metformin dose and better support and information on this treatment will reduce the incidence of side effects in these patients.
  
  
  METHODS
  The Metformin and sitAgliptin in patients with impAired glucose tolerance and a recent TIA or minor ischemic Stroke trial (MAAS trial) is a phase II, multicenter, randomized, controlled, open-label trial with blinded outcome assessment. Non-diabetic patients (n = 100) with a recent (<6 months) TIA, amaurosis fugax or minor ischemic stroke (modified Rankin scale ≤ 3) and impaired glucose tolerance, defined as 2-hour post-load glucose levels between 7.8 and 11.0 mmol/L after repeated standard oral glucose tolerance test, will be included. Patients with renal or liver impairment, heart failure, chronic hypoxic lung disease stage III-IV, history of lactate acidosis or diabetic ketoacidosis, pregnancy or breastfeeding, pancreatitis and use of digoxin will be excluded. The patients will be randomly assigned in a 1:1:2 ratio to metformin, sitagliptin or "no treatment." Patients allocated to metformin will start with 500 mg twice daily, which will be slowly increased during a 6-week period to a twice daily dose of 1000 mg. Patients allocated to sitagliptin will be treated with a daily fixed dose of 100 mg. The study has been registered as NTR 3196 in The Netherlands Trial Register. Primary outcomes include percentage still on treatment, percentage of (serious) adverse events, and the baseline adjusted difference in 2-hour post-load glucose levels at 6 months.
  
  
  CONCLUSIONS
  This study will give more information about the feasibility and safety of metformin and sitagliptin as well as the effect on 2-hour post-load glucose levels at 6 months in patients with TIA or ischemic stroke and impaired glucose tolerance.
  
  
  BACKGROUND
  NTR3196 , Date of registration: 15 December 2011.
authors.affiliation: Department of Neurology, Medisch Spectrum Twente, PO Box 50 000, Enschede, 7500, KA, The Netherlands. e.osei@mst.nl.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Osei
authors.affiliation: Department of Neurology, Erasmus Medical Center University Hospital, Rotterdam, The Netherlands. s.fonville@erasmusmc.nl.
authors.forename: Susanne
authors.initials: S
authors.lastname: Fonville
authors.affiliation: Department of Internal Medicine, Ikazia Hospital, Rotterdam, The Netherlands. aam.zandbergen@ikazia.nl.
authors.forename: Adrienne A M
authors.initials: AA
authors.lastname: Zandbergen
authors.affiliation: Department of Neurology, Medisch Spectrum Twente, PO Box 50 000, Enschede, 7500, KA, The Netherlands. p.brouwers@mst.nl.
authors.forename: Paul J A M
authors.initials: PJ
authors.lastname: Brouwers
authors.affiliation: Department of Neurology, Ikazia Hospital, Rotterdam, The Netherlands. ljmm.mulder@ikazia.nl.
authors.forename: Laus J M M
authors.initials: LJ
authors.lastname: Mulder
authors.affiliation: Department of Public Health, Erasmus Medical Center University Hospital, Rotterdam, The Netherlands. h.lingsma@erasmusmc.nl.
authors.forename: Hester F
authors.initials: HF
authors.lastname: Lingsma
authors.affiliation: Department of Neurology, Erasmus Medical Center University Hospital, Rotterdam, The Netherlands. d.dippel@erasmusmc.nl.
authors.forename: Diederik W J
authors.initials: DW
authors.lastname: Dippel
authors.affiliation: Department of Neurology, Erasmus Medical Center University Hospital, Rotterdam, The Netherlands. p.j.koudstaal@erasmusmc.nl.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Koudstaal
authors.affiliation: Department of Neurology, Erasmus Medical Center University Hospital, Rotterdam, The Netherlands. m.denhertog@mst.nl.|Department of Neurology, Medisch Spectrum Twente, PO Box 50 000, Enschede, 7500, KA, The Netherlands. m.denhertog@mst.nl.
authors.forename: Heleen M
authors.initials: HM
authors.lastname: den Hertog
mesh_terms: D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D002985:Clinical Protocols; D005240:Feasibility Studies; D018149:Glucose Intolerance / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002546:Ischemic Attack, Transient / Q000150:complications* / Q000175:diagnosis; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use*; D009426:Netherlands; D011237:Predictive Value of Tests; D012107:Research Design; D000068900:Sitagliptin Phosphate / Q000009:adverse effects / Q000627:therapeutic use*; D020521:Stroke / Q000150:complications* / Q000175:diagnosis; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D008687:Metformin; D000068900:Sitagliptin Phosphate