Effects of liraglutide on neurodegeneration, blood flow and cognition in Alzheimer´s disease - protocol for a controlled, randomized double-blinded trial

Dan Med J. 2012 Oct;59(10):A4519.

Abstract

Introduction: Type 2 diabetes (DM-2) increases the risk of developing Alzheimer´s disease (AD), and patients with AD are more likely to develop DM-2. DM-2 and AD share some pathophysiological features. In AD, amyloid-β (Aβ) is accumulated as extracellular plaques in the gray matter of the brain, while in DM-2 islet amyloid polypeptide (IAPP) is accumulated in the pancreas. Premature cellular degeneration is seen in both diseases. Glucagon-like peptide-1 (GLP-1) reduces the amount of Aβ and improves cognition in animal studies. The present study tests the hypothesis that treatment with the long-acting GLP-1 receptor agonist liraglutide affects the accumulation of Aβ in patients with AD.

Material and methods: This is a randomized, controlled, double-blinded intervention study with AD patients treated for six months with liraglutide (n = 20) or placebo (n = 20). The primary outcome is change in deposition of Aβ in the central nervous system (CNS) by Pittsburgh compound B positron emission tomography (PET). The secondary outcome is evaluation of cognition using a neuro-psychological test battery, and examination of changes in glucose uptake in the CNS by 18F-fluoro-deoxy-glucose PET. Finally, a perfusion-weighted magnetic resonance imaging with contrast will be performed to evaluate blood flow.

Conclusion: No registered drug affects the deposition of Aβ in the brain of AD patients. Our goal is to find a new therapeutic agent that alters the pathophysiology in AD patients by decreasing the formation of Aβ plaques and thereby presumably improves the cognitive function.

Funding: The trial is investigator-initiated and investigator-driven and is supported by Novo Nordisk Scandinavia.

Trial registration: ClinicalTrials.gov: NCT01469351.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Peptides / metabolism*
  • Blood Flow Velocity / drug effects*
  • Brain / metabolism*
  • Brain / physiopathology
  • Cerebrovascular Circulation / drug effects
  • Cerebrovascular Circulation / physiology*
  • Cognition / drug effects
  • Cognition / physiology*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Follow-Up Studies
  • Glucagon-Like Peptide 1 / administration & dosage
  • Glucagon-Like Peptide 1 / analogs & derivatives*
  • Humans
  • Liraglutide
  • Magnetic Resonance Imaging / methods
  • Positron-Emission Tomography
  • Treatment Outcome

Substances

  • Amyloid beta-Peptides
  • Liraglutide
  • Glucagon-Like Peptide 1

Associated data

  • ClinicalTrials.gov/NCT01469351