Exenatide Once Weekly Over 2 Years as a Potential Disease Modifying Treatment for Parkinson's Disease

NCT ID: NCT04232969

Last Updated: 2023-12-21

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 194 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-20
• Study Completion Date: 2024-07-31

Brief Summary

This study is a clinical trial in patients with Parkinson's disease (PD), of a drug called exenatide, which is already licensed for the treatment of patients with type 2 diabetes. There have been several groups that have confirmed that exenatide has beneficial effects of nerve cells when tested in the laboratory, which raises the possibility that exenatide may slow down or stop the degeneration of PD. In an open label trial in patients with PD who self administered the drug for a period of 48 weeks, the investigators have previously shown that the drug is well tolerated and shows encouraging effects on the movement and non-movement aspects of the disease. A double blind placebo controlled trial involving 60 participants was then conducted which indicated that exenatide may be a "neuroprotective" drug, i.e. one that stops the nerve cells dying in PD. The next step is therefore to confirm this "neuroprotective" effect and to see whether this effect can be reproduced in a multi-centre setting including a larger number of participants. An important objective is to explore whether any positive effects remain static or increase when the treatment is continued over a 96 week period. In order to explore this, a randomised, double blind, parallel group, placebo controlled, Phase 3 trial of Exenatide is being undertaken (Exenatide-PD3).

Detailed Description

This study is a clinical trial in patients with Parkinson's disease (PD), of a drug called exenatide, which is already licensed for the treatment of patients with type 2 diabetes. There have been several groups that have confirmed that exenatide has beneficial effects of nerve cells when tested in the laboratory, which raises the possibility that exenatide may slow down or stop the degeneration of PD. In an open label trial in patients with PD who self administered the drug for a period of 48 weeks, investigators have previously shown that the drug is well tolerated and shows encouraging effects on the movement and non-movement aspects of the disease. A double blind placebo controlled trial involving 60 participants was then conducted which indicated that exenatide may be a "neuroprotective" drug, i.e. one that stops the nerve cells dying in PD. The next step is therefore to confirm this "neuroprotective" effect and to see whether this effect can be reproduced in a multi-centre setting including a larger number of participants. An important objective is to explore whether any positive effects remain static or increase when the treatment is continued over a 96 week period.

Conditions

Parkinson's Disease

Keywords

Parkinson's Disease; Exenatide; Parkinson's research

Study Design

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

Study Groups

Exenatide

Exenatide extended release 2mg (Bydureon) once weekly for 96 weeks n=100

Group Type: ACTIVE_COMPARATOR

Exenatide extended release 2mg (Bydureon)

Intervention Type: DRUG

Subcutaneous Injection

Placebo

Exenatide extended release placebo once weekly for 96 weeks n=100

Group Type: PLACEBO_COMPARATOR

Exenatide extended release 2mg (Bydureon)

Intervention Type: DRUG

Subcutaneous Injection

Interventions

Exenatide extended release 2mg (Bydureon)

Subcutaneous Injection

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Diagnosis of Parkinson's disease.

2. Hoehn and Yahr stage ≤2.5 in the ON medication state.

3. Between 25 and 80 years of age.

4. On dopaminergic treatment for at least 4 weeks before enrolment.

5. Ability to self-administer, or to arrange carer administration of trial medication.

6. Documented informed consent to participate.

Exclusion Criteria

1. Diagnosis or suspicion of other cause for Parkinsonism.

2. Patients unable to attend the clinic visits in the practically defined OFF medication state.

3. Body mass index <18.5.

4. Known abnormality on CT or MRI brain imaging considered likely to compromise compliance with trial protocol.

5. Significant cognitive impairment defined by a score <21 on the Montreal Cognitive Assessment.

6. Concurrent severe depression defined by a score ≥16 on the Patient Health Questionnaire (PHQ-9).

7. Prior intra-cerebral surgical intervention for Parkinson's disease.

8. Previous participation in one of the following Parkinson's disease trials (Biogen SPARK trial, Prothena Pasadena trial, Sanofi Genzyme MOVES-PD trial, UDCA-PD UP Study or any other trial still considered to involve a potentially PD modifying agent).

9. Participation in another clinical trial of a device, drug or surgical treatment within the last 30 days

10. Previous exposure to exenatide.

11. Impaired renal function with creatinine clearance <50ml/min.

12. History of pancreatitis.

13. Type 1 or Type 2 diabetes mellitus.

14. Severe gastrointestinal disease (e.g. gastroparesis)

15. Hyperlipidaemia.

16. History or family history of medullary thyroid cancer (MTC).

17. Multiple endocrine neoplasia 2 (MEN2) syndrome.

18. Hypersensitivity to any of exenatide's excipients.

19. Females that are pregnant or breast feeding.

20. WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire trial period and up to 3 months after the last dose of trial medication.

21. Participants who lack the capacity to give informed consent

22. Any medical or psychiatric condition or previous conventional/experimental treatment which in the investigator's opinion compromises the potential participant's ability to participate.

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University College, London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tom Foltynie

Role: PRINCIPAL_INVESTIGATOR

University College London Comprehensive Clinical Trials Unit

Locations

University College London Hospital

London, , United Kingdom

Countries

United Kingdom

References

Vijiaratnam N, Girges C, Auld G, McComish R, King A, Skene SS, Hibbert S, Wong A, Melander S, Gibson R, Matthews H, Dickson J, Carroll C, Patrick A, Inches J, Silverdale M, Blackledge B, Whiston J, Hu M, Welch J, Duncan G, Power K, Gallen S, Kerr J, Chaudhuri KR, Batzu L, Rota S, Jabbari E, Morris H, Limousin P, Greig N, Li Y, Libri V, Gandhi S, Athauda D, Chowdhury K, Foltynie T. Exenatide once a week versus placebo as a potential disease-modifying treatment for people with Parkinson's disease in the UK: a phase 3, multicentre, double-blind, parallel-group, randomised, placebo-controlled trial. Lancet. 2025 Feb 22;405(10479):627-636. doi: 10.1016/S0140-6736(24)02808-3. Epub 2025 Feb 4.

Reference Type: DERIVED

PMID: 39919773 (View on PubMed)

Vijiaratnam N, Girges C, Auld G, Chau M, Maclagan K, King A, Skene S, Chowdhury K, Hibbert S, Morris H, Limousin P, Athauda D, Carroll CB, Hu MT, Silverdale M, Duncan GW, Chaudhuri R, Lo C, Del Din S, Yarnall AJ, Rochester L, Gibson R, Dickson J, Hunter R, Libri V, Foltynie T. Exenatide once weekly over 2 years as a potential disease-modifying treatment for Parkinson's disease: protocol for a multicentre, randomised, double blind, parallel group, placebo controlled, phase 3 trial: The 'Exenatide-PD3' study. BMJ Open. 2021 May 28;11(5):e047993. doi: 10.1136/bmjopen-2020-047993.

Reference Type: DERIVED

PMID: 34049922 (View on PubMed)

Related Links

https://www.ucl.ac.uk/comprehensive-clinical-trials-unit/research-projects/2021/jan/exenatide-parkinsons-disease

Sponsor Trial web link

Other Identifiers

18/0320

Identifier Type: -

Identifier Source: org_study_id