Evaluating Liraglutide in Alzheimer's Disease

NCT01843075 | Unknown Phase 2 DMC

• 1 other identifier: U1111-1131-9252
• Study Type: interventional
• Target: 204
• Locations: 1 country
• Sites: 1

Brief Summary

This is a 12-month, multicentre randomised double-blind placebo-controlled Phase IIb study in patients with mild Alzheimer's dementia (AD). Patients will be randomised on a 1:1 ratio to receive liraglutide or matching placebo.

Conditions

Alzheimer's Disease

Outcome Measures

Primary Outcomes (1)

• The change in cerebral glucose metabolic rate

  The change in cerebral glucose metabolic rate from baseline to follow up (12 months) in the treatment group compared with the placebo group.

  12 months

Secondary Outcomes (5)

• The change in z-scores for the ADAS Exec, MRI changes, microglial activation, and CSF markers

  12 months

• The incidence and severity of treatment emergent adverse events

  12 months

• The change in microglial activation

  12 months

• The change in tau deposition

  12 months

• The change in cortical amyloid

  12 months

Study Arms (2)

Liraglutide

EXPERIMENTAL

Daily administration of 1.8 mg liraglutide by subcutaneous injection

Drug: Liraglutide

Placebo

PLACEBO COMPARATOR

Daily administration of matched placebo by subcutaneous injection

Drug: Placebo

Interventions

Liraglutide DRUG

Daily subcutaneous injection

Also known as: Victoza

Liraglutide

Placebo DRUG

Daily subcutaneous injection

Placebo

Eligibility Criteria

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

You may qualify if:

• Capable of giving and capacity to give informed consent
• An individual who can act as a reliable study partner with regular contact (combination of face to face visits / telephone contact acceptable) who has sufficient subject interaction to provide meaningful input into rating scales and, if necessary, supervise or perform the injections, as judged by the investigator
• Diagnosis of Probable Alzheimer's disease according to Dubois criteria (Dubois, Feldman et al. 2007) or National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria
• Age from 50 years
• Mini-Mental State Examination (MMSE) score of ≥20 and CDR-Global score of 0.5 or 1
• Rosen Modified Hachinski Ischemic score ≤4
• On stable medication for 2 months before the screening visit; on or off cholinesterase inhibitors
• Fluency in English and evidence of adequate premorbid intellectual functioning
• Likely to be able to participate in all scheduled evaluations and complete all required tests

You may not qualify if:

• Patients on treatment for diabetes mellitus
• Any contraindications to the use of liraglutide as per the Summary of Product Characteristics (hepatic impairment, renal impairment with CKD stage 4 and above (eGFR \<30 ml/min/1.73m2), inflammatory bowel disease). Patients with eGFR less than 45 ml/min/1.73m2 will have the renal function monitored very closely
• Significant neurological disease other than AD that may affect cognition
• MRI/CT showing unambiguous aetiological evidence of cerebrovascular disease with regard to their dementia or vascular dementia fulfilling NINCDS-AIREN criteria
• Current presence of a clinically significant major psychiatric disorder (e.g., Major Depressive Disorder) according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)
• Current clinically significant systemic illness that is likely to result in deterioration of the patient's condition or affect the patient's safety during the study
• History of epilepsy, where seizures or treatment could have contributed to cognitive impairment
• Treatment with immunosuppressive medications (e.g. systemic corticosteroids) within the last 90 days (topical and nasal corticosteroids and inhaled corticosteroids for asthma are permitted) or chemotherapeutic agents for malignancy within the last 3 years
• Myocardial infarction within the last 1 year
• History of cancer within the last 5 years, except localised skin cancer
• Other clinically significant abnormality on physical, neurological or laboratory examination that could compromise the study or be detrimental to the patient
• History of alcohol or drug dependence or abuse within the last 2 years
• Current use of anticonvulsant, anti-Parkinson's, anticoagulant (excluding the use of aspirin 325 mg/day or less) or narcotic medications. Subjects on anticoagulants will be allowed, but will not have an arterial line inserted
• Use of experimental medications for AD or any other investigational medication or device within 60 days. Patients who have been involved in a monoclonal antibody study are excluded unless it is known that they were receiving placebo in that trial
• Women of childbearing potential. Women who could become pregnant will be required to use adequate contraception throughout the trial

Sponsors & Collaborators

• Imperial College London: lead
• King's College Hospital NHS Trust: collaborator
• University of Oxford: collaborator
• University of Southampton: collaborator
• Avon and Wiltshire Mental Health Partnership NHS Trust: collaborator

Study Sites (1)

Imperial College, Hammersmith Hospital

London, W12 0NN, United Kingdom

Location

Related Publications (3)

• Edison P, Femminella GD, Ritchie C, Nowell J, Holmes C, Walker Z, Ridha B, Raza S, Livingston NR, Frangou E, Love S, Williams G, Lawrence R, Mcfarlane B, Archer H, Coulthard E, Underwood BR, Koranteng P, Karim S, Bannister C, Perneczky R, Prasanna A, Junaid K, McGuinness B, Nilforooshan R, Macharouthu A, Donaldson A, Thacker S, Russell G, Malik N, Mate V, Knight L, Kshemendran S, Holscher C, Mansouri A, Chester-Jones M, Holmes J, Tan T, Williams S, Ashraf A, Brooks DJ, Harrison J, Hinz R, Tadros G, Passmore AP, Ballard C. Liraglutide in mild to moderate Alzheimer's disease: a phase 2b clinical trial. Nat Med. 2026 Jan;32(1):353-361. doi: 10.1038/s41591-025-04106-7. Epub 2025 Dec 1.

  PMID: 41326666 DERIVED

• Femminella GD, Frangou E, Love SB, Busza G, Holmes C, Ritchie C, Lawrence R, McFarlane B, Tadros G, Ridha BH, Bannister C, Walker Z, Archer H, Coulthard E, Underwood BR, Prasanna A, Koranteng P, Karim S, Junaid K, McGuinness B, Nilforooshan R, Macharouthu A, Donaldson A, Thacker S, Russell G, Malik N, Mate V, Knight L, Kshemendran S, Harrison J, Holscher C, Brooks DJ, Passmore AP, Ballard C, Edison P. Evaluating the effects of the novel GLP-1 analogue liraglutide in Alzheimer's disease: study protocol for a randomised controlled trial (ELAD study). Trials. 2019 Apr 3;20(1):191. doi: 10.1186/s13063-019-3259-x. Erratum In: Trials. 2020 Jul 19;21(1):660. doi: 10.1186/s13063-020-04608-4.

  PMID: 30944040 DERIVED

• 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

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

• Paul Edison, PhD FRCPI

  Imperial College London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• 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: April 24, 2013
• First Posted: April 30, 2013
• Study Start: January 1, 2014
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2019
• Last Updated: June 10, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)