Exenatide Once Weekly Over 2 Years as a Potential Disease Modifying Treatment for Parkinson's Disease (Exenatide-PD3)

• ClinicalTrials.gov Identifier: NCT04232969
• Recruitment Status: Active, not recruiting
• First Posted: January 18, 2020
• Last Update Posted: May 19, 2022
• Sponsor: University College, London
• Information provided by (Responsible Party): University College, London

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Parkinson's Disease	Drug: Exenatide extended release 2mg (Bydureon)	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 194 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: A randomised, double blind, parallel group, placebo controlled, Phase 3 trial of Exenatide once weekly over 2 years as a potential disease modifying treatment for Parkinson's disease.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Double Blind
• Primary Purpose: Treatment
• Official Title: A Randomised, Double Blind, Parallel Group, Placebo Controlled, Phase 3 Trial of Exenatide Once Weekly Over 2 Years as a Potential Disease Modifying Treatment for Parkinson's Disease
• Actual Study Start Date: January 20, 2020
• Estimated Primary Completion Date: February 24, 2024
• Estimated Study Completion Date: June 30, 2024

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Exenatide; Exenatide extended release 2mg (Bydureon) once weekly for 96 weeks n=100	Drug: Exenatide extended release 2mg (Bydureon); Subcutaneous Injection
Placebo Comparator: Placebo; Exenatide extended release placebo once weekly for 96 weeks n=100	Drug: Exenatide extended release 2mg (Bydureon); Subcutaneous Injection

Outcome Measures

Primary Outcome Measures :

1. Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part 3 [ Time Frame: 96 weeks ]
   Comparison of MDS-UPDRS part 3 motor sub-score in the practically defined OFF medication state at 96 weeks between participants according to treatment allocation. Min value- 0 Max Value- 108. Higher score indicative of worse outcome.

Secondary Outcome Measures :

1. Movement Disorder Society Unified Parkinson's Disease Rating Scale part 1,2, and 4 ON medication scores. [ Time Frame: 96 weeks ]
   Questionnaire. Section I: 16 points; Section II: 52; Section IV: 23. Higher score indicative of worse outcome.
2. Timed Walk assessment ON and OFF medication [ Time Frame: 96 weeks ]
   Assessment with research team
3. Montreal Cognitive Assessment [ Time Frame: 96 weeks ]
   Questionnaire. Maximum Score= 30. Lower scores indicative of worse outcome.
4. Unified Dyskinesia Rating Scale (UDysRS) [ Time Frame: 96 weeks ]
   Questionnaire. The UDysRS has four parts: I: Historical Disability (patient perceptions) of On-Dyskinesia impact (maximum 44 points); II: Historical Disability (patient perceptions) of Off-Dystonia impact (maximum 16 points); III: Objective Impairment (dyskinesia severity, anatomical distribution over seven body regions, and type (choreic or dystonic) based on four activities observed or video-recorded (28 points); IV: Objective Disability based on Part III activities (maximum 16 points). Higher scores= worse outcomes
5. Patient Health Questionnaire-9 (PHQ-9) [ Time Frame: 96 weeks ]
   Questionnaire. Depression Severity: 0-4 none, 5-9 mild, 10-14 moderate, 15-19 moderately severe, 20-27 severe. Max Score= 27. Higher Score= worse outcome
6. Parkinson's Disease 39 item Quality of life questionnaire [ Time Frame: 96 weeks ]
   This questionnaire assesses how often people affected by Parkinson's experience difficulties across 8 dimensions of daily living. The 39 item questionnaire offers a patient reported measure of health status and quality of life and is the most frequently used disease-specific health status measure. Higher score= worse outcome.
7. Non-Motor Symptoms Scale (NMSS) [ Time Frame: 96 weeks ]
   Questionnaire. The Non-Motor Symptoms Scale (NMSS) is a 30-item rater-based scale to assess a wide range of non-motor symptoms in patients with Parkinson's disease (PD). The NMSS measures the severity and frequency of non-motor symptoms across nine dimensions. The scale can be used for patients at all stages of PD. Higher score indicative of worse outcome. NMSS total score is 0 to 360.
8. Levodopa Equivalent Dose [ Time Frame: 96 weeks ]
   Assessment with Research Team
9. 3 day Hauser diary of Parkinson's Disease State [ Time Frame: 96 weeks ]
   Participant take Home questionnaire. (Time-On, Off, Non troublesome Dyskinesia, Troublesome dyskinesia, Asleep). Higher total scores indicate more severe motor signs of Parkinson's.
10. Safety and tolerability of exenatide as indicated by changes in pulse (bpm) [ Time Frame: 96 weeks ]
    Vital Signs
11. Safety and tolerability of exenatide as indicated by changes in blood pressure (mmHg) [ Time Frame: 96 weeks ]
    Vital Signs
12. Safety and tolerability of exenatide as indicated by changes in Body Mass Index (weight and height will be combined to report BMI in kg/m^2) [ Time Frame: 96 weeks ]
    Vital Signs
13. Safety and tolerability of exenatide as indicated by changes in Red Blood Cell Count (10^12/L) [ Time Frame: 96 weeks ]
    Full Blood Count
14. Safety and tolerability of exenatide as indicated by changes in White Blood Cell Count (10^9/L) [ Time Frame: 96 weeks ]
    Full Blood Count
15. Safety and tolerability of exenatide as indicated by changes in Haemoglobin (g/dL) [ Time Frame: 96 weeks ]
    Full Blood Count
16. Safety and tolerability of exenatide as indicated by changes in Haematocrit (%) [ Time Frame: 96 weeks ]
    Full Blood Count
17. Safety and tolerability of exenatide as indicated by changes in Platelets (10^9/L) [ Time Frame: 96 weeks ]
    Full Blood Count
18. Safety and tolerability of exenatide as indicated by changes in Neutrophils (10^9/L) [ Time Frame: 96 weeks ]
    Full Blood Count
19. Safety and tolerability of exenatide as indicated by changes in Eosinophils (10^9/L) [ Time Frame: 96 weeks ]
    Full Blood Count
20. Safety and tolerability of exenatide as indicated by changes in Basophils (10^9/L) [ Time Frame: 96 weeks ]
    Full Blood Count
21. Safety and tolerability of exenatide as indicated by changes in Lymphocytes (10^9/L) [ Time Frame: 96 weeks ]
    Full Blood Count
22. Safety and tolerability of exenatide as indicated by changes in Monocytes (10^9/L) [ Time Frame: 96 weeks ]
    Full Blood Count
23. Safety and tolerability of exenatide as indicated by changes in Prothrombin Time (secs) [ Time Frame: 96 weeks ]
    Blood Tests (Coagulation)
24. Safety and tolerability of exenatide as indicated by changes in International Normalized Ratio (Calculated from Prothrombin Time) [ Time Frame: 96 weeks ]
    Blood Tests (Coagulation)
25. Safety and tolerability of exenatide as indicated by changes in Activated Partial Thromboplastin Time (secs) [ Time Frame: 96 weeks ]
    Blood Tests (Coagulation)
26. Safety and tolerability of exenatide as indicated by changes in Thrombin Time (secs) [ Time Frame: 96 weeks ]
    Blood Tests (Coagulation)
27. Safety and tolerability of exenatide as indicated by changes in Fibrinogen (g/L) [ Time Frame: 96 weeks ]
    Blood Tests (Coagulation)
28. Safety and tolerability of exenatide as indicated by changes in Glycated Haemoglobin (% of Haemoglobin) [ Time Frame: 96 weeks ]
    Blood Tests (Blood Sugar Levels / Diabetes Testing)
29. Safety and tolerability of exenatide as indicated by changes in Sodium (mmol/L) [ Time Frame: 96 weeks ]
    Biochemistry
30. Safety and tolerability of exenatide as indicated by changes in Potassium (mmol/L) [ Time Frame: 96 weeks ]
    Biochemistry
31. Safety and tolerability of exenatide as indicated by changes in Urea (mmol/L) [ Time Frame: 96 weeks ]
    Biochemistry
32. Safety and tolerability of exenatide as indicated by changes in Creatinine (µmol/L) [ Time Frame: 96 weeks ]
    Biochemistry
33. Safety and tolerability of exenatide as indicated by changes in Creatinine Clearance (ml/min) [ Time Frame: 96 weeks ]
    Biochemistry
34. Safety and tolerability of exenatide as indicated by changes in Total Bilirubin (µmol/L) [ Time Frame: 96 weeks ]
    Biochemistry
35. Safety and tolerability of exenatide as indicated by changes in Alkaline phosphatase (IU/L) [ Time Frame: 96 weeks ]
    Biochemistry
36. Safety and tolerability of exenatide as indicated by changes in Alanine transaminase (IU/L) [ Time Frame: 96 weeks ]
    Biochemistry
37. Safety and tolerability of exenatide as indicated by changes in Aspartate Aminotransferase (IU/L) [ Time Frame: 96 weeks ]
    Biochemistry
38. Safety and tolerability of exenatide as indicated by changes in Serum Amylase (U/L) [ Time Frame: 96 weeks ]
    Biochemistry
39. Safety and tolerability of exenatide as indicated by changes in Thyroid Stimulating Hormone (mIU/L) [ Time Frame: 96 weeks ]
    Biochemistry
40. Safety and tolerability of exenatide as indicated by changes in Thyroxin (T4) (pmol/L) [ Time Frame: 96 weeks ]
    Biochemistry
41. Safety and tolerability of exenatide as indicated by changes in Triglycerides (mg/dL) [ Time Frame: 96 weeks ]
    Biochemistry (Fasting)
42. Safety and tolerability of exenatide as indicated by changes in Cholesterol (mg/dL) [ Time Frame: 96 weeks ]
    Biochemistry (Fasting)
43. Safety and tolerability of exenatide as indicated by changes in Glucose (mmol/L) [ Time Frame: 96 weeks ]
    Biochemistry (Fasting)
44. Safety and tolerability of exenatide as indicated by changes in Insulin (IU/L) [ Time Frame: 96 weeks ]
    Biochemistry (Fasting)
45. Safety and tolerability of exenatide as indicated by the occurrence / severity of Adverse Events [ Time Frame: 96 weeks ]
    Ongoing Safety Reporting

Eligibility Criteria

• Ages Eligible for Study: 25 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United Kingdom

University College London Hospital

London, United Kingdom

Sponsors and Collaborators

University College, London

Investigators

• Principal Investigator: Tom Foltynie; University College London Comprehensive Clinical Trials Unit

More Information

Additional Information:

Sponsor Trial web link 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: University College, London
• ClinicalTrials.gov Identifier: NCT04232969
• Other Study ID Numbers: 18/0320
• First Posted: January 18, 2020
• Last Update Posted: May 19, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University College, London:

Parkinson's Disease; Exenatide; Parkinson's research

Additional relevant MeSH terms:

Parkinson Disease; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Exenatide; Hypoglycemic Agents; Physiological Effects of Drugs; Anti-Obesity Agents; Incretins; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists