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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04232969
Recruitment Status : Not yet recruiting
First Posted : January 18, 2020
Last Update Posted : January 18, 2020
Sponsor:
Information provided by (Responsible Party):
University College, London

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, we 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 subcutaneous injection (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, we 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 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
Estimated Study Start Date : January 20, 2020
Estimated Primary Completion Date : September 30, 2023
Estimated Study Completion Date : September 30, 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Exenatide

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

Placebo Comparator: Placebo
Exenatide extended release placebo subcutaneous injection once weekly for 96 weeks n=100
Drug: Exenatide extended release 2mg subcutaneous injection (Bydureon)
Subcutaneous Injection




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. Section I: 16 points; Section II: 52; Section IV: 23. Higher score indicative of worse outcome [ Time Frame: 96 weeks ]
    Questionnaire

  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.

  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)

  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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04232969


Contacts
Layout table for location contacts
Contact: Professor Tom Foltynie 020 3448 8726 t.foltynie@ucl.ac.uk
Contact: Grace Auld 02076799895 g.auld@ucl.ac.uk

Locations
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United Kingdom
University College London Hospital
London, United Kingdom
Principal Investigator: Tom Foltynie, BSc, MBBS, MRCP, PhD         
Sponsors and Collaborators
University College, London
Investigators
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Principal Investigator: Tom Foltynie University College London Comprehensive Clinical Trials Unit

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Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT04232969    
Other Study ID Numbers: 18/0320
First Posted: January 18, 2020    Key Record Dates
Last Update Posted: January 18, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Additional relevant MeSH terms:
Layout table for MeSH terms
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Exenatide
Hypoglycemic Agents
Physiological Effects of Drugs
Anti-Obesity Agents
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists