Evaluating Liraglutide in Alzheimer's Disease

NCT ID: NCT01843075

Last Updated: 2019-06-10

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 204 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-31
• Study Completion Date: 2019-12-31

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.

Detailed Description

The investigators aim to recruit patients with mild Alzheimer's dementia as defined by the National Institute of Neurological and Communicative Disorders and Stroke - Alzheimer's Disease and Related Disorder Association (NINCDS-ADRDA) Criteria for Probable Alzheimer's Dementia or meeting Dubois criteria for early AD, with Mini Mental State Evaluation score of at least 20 out of a maximum of 30 and a CDR Global score of 0.5 or 1.

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Conditions

Alzheimer's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Liraglutide

Daily administration of 1.8 mg liraglutide by subcutaneous injection

Group Type: EXPERIMENTAL

Liraglutide

Intervention Type: DRUG

Daily subcutaneous injection

Placebo

Daily administration of matched placebo by subcutaneous injection

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Daily subcutaneous injection

Interventions

Liraglutide

Daily subcutaneous injection

Intervention Type: DRUG

Placebo

Daily subcutaneous injection

Intervention Type: DRUG

Other Intervention Names

Victoza

Eligibility Criteria

Inclusion Criteria

1. Capable of giving and capacity to give informed consent

2. 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

3. 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

4. Age from 50 years

5. Mini-Mental State Examination (MMSE) score of ≥20 and CDR-Global score of 0.5 or 1

6. Rosen Modified Hachinski Ischemic score ≤4

7. On stable medication for 2 months before the screening visit; on or off cholinesterase inhibitors

8. Fluency in English and evidence of adequate premorbid intellectual functioning

9. Likely to be able to participate in all scheduled evaluations and complete all required tests

Exclusion Criteria

1. Patients on treatment for diabetes mellitus

2. 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

3. Significant neurological disease other than AD that may affect cognition

4. MRI/CT showing unambiguous aetiological evidence of cerebrovascular disease with regard to their dementia or vascular dementia fulfilling NINCDS-AIREN criteria

5. 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)

6. 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

7. History of epilepsy, where seizures or treatment could have contributed to cognitive impairment

8. 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

9. Myocardial infarction within the last 1 year

10. History of cancer within the last 5 years, except localised skin cancer

11. Other clinically significant abnormality on physical, neurological or laboratory examination that could compromise the study or be detrimental to the patient

12. History of alcohol or drug dependence or abuse within the last 2 years

13. 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

14. 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

15. Women of childbearing potential. Women who could become pregnant will be required to use adequate contraception throughout the trial

16. Patients with a personal or family history of medullary thyroid carcinoma (MTC) and patients with multiple endocrine neoplasia type 2 (MEN2)

17. Any contraindications to MRI scanning

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

King's College Hospital NHS Trust

OTHER

Sponsor Role: collaborator

University of Oxford

OTHER

Sponsor Role: collaborator

University of Southampton

OTHER

Sponsor Role: collaborator

Avon and Wiltshire Mental Health Partnership NHS Trust

OTHER_GOV

Sponsor Role: collaborator

Imperial College London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Paul Edison, PhD FRCPI

Role: PRINCIPAL_INVESTIGATOR

Imperial College London

Locations

Imperial College, Hammersmith Hospital

London, , United Kingdom

Countries

United Kingdom

References

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.

Reference Type: DERIVED

PMID: 30944040 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27871675 (View on PubMed)

Other Identifiers

U1111-1131-9252

Identifier Type: -

Identifier Source: org_study_id