Clinical trial NCT04232969: Exenatide Once Weekly Over 2 Years as a Potential Disease Modifying Treatment for Parkinson's Disease
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Parkinson's Disease
Keywords: Parkinson's Disease
Exenatide
Parkinson's research
Lead sponsor: University College, London
Sponsor class: OTHER
First posted: 2020-01-18
Enrollment: 194
Sex: ALL
Minimum age (years): 25
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part 3
timeFrame: 96 weeks
Secondary outcomes:
measure: Movement Disorder Society Unified Parkinson's Disease Rating Scale part 1,2, and 4 ON medication scores.
timeFrame: 96 weeks
measure: Timed Walk assessment ON and OFF medication
timeFrame: 96 weeks
measure: Montreal Cognitive Assessment
timeFrame: 96 weeks
measure: Unified Dyskinesia Rating Scale (UDysRS)
timeFrame: 96 weeks
measure: Patient Health Questionnaire-9 (PHQ-9)
timeFrame: 96 weeks
measure: Parkinson's Disease 39 item Quality of life questionnaire
timeFrame: 96 weeks
measure: Non-Motor Symptoms Scale (NMSS)
timeFrame: 96 weeks
measure: Levodopa Equivalent Dose
timeFrame: 96 weeks
measure: 3 day Hauser diary of Parkinson's Disease State
timeFrame: 96 weeks
measure: Safety and tolerability of exenatide as indicated by changes in pulse (bpm)
timeFrame: 96 weeks
measure: Safety and tolerability of exenatide as indicated by changes in blood pressure (mmHg)
timeFrame: 96 weeks
measure: 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)
timeFrame: 96 weeks
measure: Safety and tolerability of exenatide as indicated by changes in Red Blood Cell Count (10^12/L)
timeFrame: 96 weeks
measure: Safety and tolerability of exenatide as indicated by changes in White Blood Cell Count (10^9/L)
timeFrame: 96 weeks
measure: Safety and tolerability of exenatide as indicated by changes in Haemoglobin (g/dL)
timeFrame: 96 weeks
measure: Safety and tolerability of exenatide as indicated by changes in Haematocrit (%)
timeFrame: 96 weeks
measure: Safety and tolerability of exenatide as indicated by changes in Platelets (10^9/L)
timeFrame: 96 weeks
measure: Safety and tolerability of exenatide as indicated by changes in Neutrophils (10^9/L)
timeFrame: 96 weeks
measure: Safety and tolerability of exenatide as indicated by changes in Eosinophils (10^9/L)
timeFrame: 96 weeks
measure: Safety and tolerability of exenatide as indicated by changes in Basophils (10^9/L)
timeFrame: 96 weeks
measure: Safety and tolerability of exenatide as indicated by changes in Lymphocytes (10^9/L)
timeFrame: 96 weeks
measure: Safety and tolerability of exenatide as indicated by changes in Monocytes (10^9/L)
timeFrame: 96 weeks
measure: Safety and tolerability of exenatide as indicated by changes in Prothrombin Time (secs)
timeFrame: 96 weeks
measure: Safety and tolerability of exenatide as indicated by changes in International Normalized Ratio (Calculated from Prothrombin Time)
timeFrame: 96 weeks
measure: Safety and tolerability of exenatide as indicated by changes in Activated Partial Thromboplastin Time (secs)
timeFrame: 96 weeks
measure: Safety and tolerability of exenatide as indicated by changes in Thrombin Time (secs)
timeFrame: 96 weeks
measure: Safety and tolerability of exenatide as indicated by changes in Fibrinogen (g/L)
timeFrame: 96 weeks
measure: Safety and tolerability of exenatide as indicated by changes in Glycated Haemoglobin (% of Haemoglobin)
timeFrame: 96 weeks
measure: Safety and tolerability of exenatide as indicated by changes in Sodium (mmol/L)
timeFrame: 96 weeks
measure: Safety and tolerability of exenatide as indicated by changes in Potassium (mmol/L)
timeFrame: 96 weeks
measure: Safety and tolerability of exenatide as indicated by changes in Urea (mmol/L)
timeFrame: 96 weeks
measure: Safety and tolerability of exenatide as indicated by changes in Creatinine (µmol/L)
timeFrame: 96 weeks
measure: Safety and tolerability of exenatide as indicated by changes in Creatinine Clearance (ml/min)
timeFrame: 96 weeks
measure: Safety and tolerability of exenatide as indicated by changes in Total Bilirubin (µmol/L)
timeFrame: 96 weeks
measure: Safety and tolerability of exenatide as indicated by changes in Alkaline phosphatase (IU/L)
timeFrame: 96 weeks
measure: Safety and tolerability of exenatide as indicated by changes in Alanine transaminase (IU/L)
timeFrame: 96 weeks
measure: Safety and tolerability of exenatide as indicated by changes in Aspartate Aminotransferase (IU/L)
timeFrame: 96 weeks
measure: Safety and tolerability of exenatide as indicated by changes in Serum Amylase (U/L)
timeFrame: 96 weeks
measure: Safety and tolerability of exenatide as indicated by changes in Thyroid Stimulating Hormone (mIU/L)
timeFrame: 96 weeks
measure: Safety and tolerability of exenatide as indicated by changes in Thyroxin (T4) (pmol/L)
timeFrame: 96 weeks
measure: Safety and tolerability of exenatide as indicated by changes in Triglycerides (mg/dL)
timeFrame: 96 weeks
measure: Safety and tolerability of exenatide as indicated by changes in Cholesterol (mg/dL)
timeFrame: 96 weeks
measure: Safety and tolerability of exenatide as indicated by changes in Glucose (mmol/L)
timeFrame: 96 weeks
measure: Safety and tolerability of exenatide as indicated by changes in Insulin (IU/L)
timeFrame: 96 weeks
measure: Safety and tolerability of exenatide as indicated by the occurrence / severity of Adverse Events
timeFrame: 96 weeks
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: University College London Hospital
Study officials:
affiliation: University College London Comprehensive Clinical Trials Unit
name: Tom Foltynie
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.