Identifying Potential Effects of Liraglutide on Degenerative Changes

NCT01469351 | Completed DMC

• 1 other identifier: 2011-000794-31
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

Today Alzheimers disease can not be cured. Animal experiments have shown that the hormone GLP-1 can improve memory in Alzheimer-prone mice. The investigators hypothesis is that a 6-month treatment with the GLP-1 receptor stimulating drug liraglutide will reduce the intracerebral amyloid deposition in the central nervous system (CNS) in patients with Alzheimer's disease (AD) and thereby reduce the clinical symptoms of the disease.

Conditions

Alzheimers Disease

Keywords

Alzheimers disease

Outcome Measures

Primary Outcomes (1)

• PIB PET scan

  Primarily to investigate whether 26 weeks of treatment with GLP-1 receptor liraglutide (Victoza ®) will change the intra-cerebral amyloid deposit in the CNS in patients with Alzheimer's disease assessed by PIB PET scan.

  PIB PET-scan at baseline and after 26 weeks

Secondary Outcomes (2)

• Neuro-psychological tests

  At baseline, after 12 weeks and after 26 weeks

• FDG PET Scan

  FDG PET-scan at baseline and after 26 weeks

Study Arms (2)

Drug

ACTIVE COMPARATOR

the GLP-1 receptor analog liraglutide is the active drug. The dose is 1.8mg daily

Drug: Liraglutide

placebo

PLACEBO COMPARATOR

non active intervention

Drug: non-active study drug

Interventions

Liraglutide DRUG

Liraglutide (Victoza ®), human GLP-1 analog produced using recombinant DNA technology in saccharomyces cerevisiae. Victoza ® is registered and approved for the treatment of type 2 diabetes. Victoza ® stimulates glucose-dependent insulin secretion from β-cells and inhibits glucagon secretion, slows ventricle emptying and reduces body weight and body fat mass by affecting appetite regulation. Form of administration: Liraglutide is a clear injection fluid, which comes in a prefilled disposable pen. 1 ml contains 6 mg of liraglutide in sterile water. There is added disodium phosphate and propylene glycol and the preservative phenol. A filled pen contains 18mg liraglutide in 3ml. NovoFine® needles are used.

Drug

non-active study drug DRUG

placebo

placebo

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent before study-related activity
• Adult competent persons
• Diagnosed with diagnosed Alzheimer's disease. With a MMSE score between 18-21 the diagnosis should be entirely based on the clinic, while diagnosis by MMSE with a score \> 22 should be diagnosed by spinal puncture
• Age ≥ 50 years and ≤ 80 years
• Caucasians

You may not qualify if:

• Diabetes mellitus
• Clinically significant liver (s-ALT \> 2 times upper reference or creatinine-clearance \< 30 mL / min, assessed on Cockcroft-Gault normogram)
• Clinically significant anemia
• Other clinically relevant abnormal biochemical value
• Current or former presence of one of the following diseases with clinical relevance:
• another CNS-illness other than diagnosed depression treated with SSRI or SSRI similar drugs.
• liver disease
• kidney disease
• endocrinological disease other than well controlled hypothyroidism
• Current or history of chronic or acute pancreatitis
• Any disease which the investigators believe may affect the study
• Patients treated with TCA or neuroleptics
• Known abuse of alcohol or drugs
• Known allergy to liraglutide or any of the other components (disodium phosphate dihydrate, propylene glycol and phenol)
• Persons who within a period of the last 2 years have participated in scientific experiments involving the use of isotopes, or who have had greater diagnostic tests performed using applied ionizing radiation

Sponsors & Collaborators

• University of Aarhus: lead

Study Sites (1)

Aarhus University

Aarhus, 8000, Denmark

Location

Related Publications (7)

• Abbas T, Faivre E, Holscher C. Impairment of synaptic plasticity and memory formation in GLP-1 receptor KO mice: Interaction between type 2 diabetes and Alzheimer's disease. Behav Brain Res. 2009 Dec 14;205(1):265-71. doi: 10.1016/j.bbr.2009.06.035. Epub 2009 Jun 30.

  PMID: 19573562 BACKGROUND

• Cole AR, Astell A, Green C, Sutherland C. Molecular connexions between dementia and diabetes. Neurosci Biobehav Rev. 2007;31(7):1046-63. doi: 10.1016/j.neubiorev.2007.04.004. Epub 2007 Apr 24.

  PMID: 17544131 BACKGROUND

• Dimou E, Booij J, Rodrigues M, Prosch H, Attems J, Knoll P, Zajicek B, Dudczak R, Mostbeck G, Kuntner C, Langer O, Bruecke T, Mirzaei S. Amyloid PET and MRI in Alzheimer's disease and mild cognitive impairment. Curr Alzheimer Res. 2009 Jun;6(3):312-9. doi: 10.2174/156720509788486563.

  PMID: 19519314 BACKGROUND

• During MJ, Cao L, Zuzga DS, Francis JS, Fitzsimons HL, Jiao X, Bland RJ, Klugmann M, Banks WA, Drucker DJ, Haile CN. Glucagon-like peptide-1 receptor is involved in learning and neuroprotection. Nat Med. 2003 Sep;9(9):1173-9. doi: 10.1038/nm919. Epub 2003 Aug 17.

  PMID: 12925848 BACKGROUND

• Muscogiuri G, DeFronzo RA, Gastaldelli A, Holst JJ. Glucagon-like Peptide-1 and the Central/Peripheral Nervous System: Crosstalk in Diabetes. Trends Endocrinol Metab. 2017 Feb;28(2):88-103. doi: 10.1016/j.tem.2016.10.001. Epub 2016 Oct 27.

  PMID: 27871675 DERIVED

• Gejl M, Gjedde A, Egefjord L, Moller A, Hansen SB, Vang K, Rodell A, Braendgaard H, Gottrup H, Schacht A, Moller N, Brock B, Rungby J. In Alzheimer's Disease, 6-Month Treatment with GLP-1 Analog Prevents Decline of Brain Glucose Metabolism: Randomized, Placebo-Controlled, Double-Blind Clinical Trial. Front Aging Neurosci. 2016 May 24;8:108. doi: 10.3389/fnagi.2016.00108. eCollection 2016.

  PMID: 27252647 DERIVED

• Egefjord L, Gejl M, Moller A, Braendgaard H, Gottrup H, Antropova O, Moller N, Poulsen HE, Gjedde A, Brock B, Rungby J. 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.

  PMID: 23158895 DERIVED

Related Links

• information about Alzheimers disease

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Liraglutide

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Birgitte Brock, MD phD

  University of Aarhus

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 2011
• First Posted: November 10, 2011
• Study Start: January 1, 2012
• Primary Completion: April 1, 2013
• Study Completion: April 1, 2013
• Last Updated: April 19, 2013

Record last verified: 2013-04

Locations

DK (1)