A Natural History Study of Patients With G2019S LRRK2 Parkinson's Disease

NCT ID: NCT05349019

Last Updated: 2023-01-18

Basic Information

• Recruitment Status: TERMINATED
• Total Enrollment: 22 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-05-02
• Study Completion Date: 2022-08-05

Brief Summary

To characterize using a participant centered decentralized (at home) study featuring wearable technology and telemedicine to study disease change over time in patients with PD caused by the G2019S mutation in the LRRK2 gene and to identify a clinical endpoint(s) for disease modifying experimental therapy trials.

Conditions

Patients With Parkinson's Disease (PD) Caused by the p.Gly2019Ser (G2019S) Pathogenic Mutation of the Leucine-Rich Repeat Kinase 2 (LRRK2) Gene

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Part A/Sub Cohort A1

15 healthy participants 18-35 years of age

Observational

Intervention Type: OTHER

This is an observational study to investigate the natural history of G2019S LRRK2 PD using traditional and digital methodology (digital phenotyping). Study conduct will be decentralized (at home as much as possible) consisting of two parts: Part A with Healthy Volunteers (HV) participants and Part B in patients with G2019S LRRK2 PD.

Part A/Sub Cohort A2

15 healthy participants 65-80 years of age

Observational

Intervention Type: OTHER

This is an observational study to investigate the natural history of G2019S LRRK2 PD using traditional and digital methodology (digital phenotyping). Study conduct will be decentralized (at home as much as possible) consisting of two parts: Part A with Healthy Volunteers (HV) participants and Part B in patients with G2019S LRRK2 PD.

Part A/Sub Cohort A3

Control group age and sex matched to the PD participants in Part B of the study

Observational

Intervention Type: OTHER

This is an observational study to investigate the natural history of G2019S LRRK2 PD using traditional and digital methodology (digital phenotyping). Study conduct will be decentralized (at home as much as possible) consisting of two parts: Part A with Healthy Volunteers (HV) participants and Part B in patients with G2019S LRRK2 PD.

Part B

60 participants with a confirmed diagnosis of Parkinson's disease and a heterozygous G2019S mutation in the LRRK2 gene

Observational

Intervention Type: OTHER

This is an observational study to investigate the natural history of G2019S LRRK2 PD using traditional and digital methodology (digital phenotyping). Study conduct will be decentralized (at home as much as possible) consisting of two parts: Part A with Healthy Volunteers (HV) participants and Part B in patients with G2019S LRRK2 PD.

Interventions

Observational

This is an observational study to investigate the natural history of G2019S LRRK2 PD using traditional and digital methodology (digital phenotyping). Study conduct will be decentralized (at home as much as possible) consisting of two parts: Part A with Healthy Volunteers (HV) participants and Part B in patients with G2019S LRRK2 PD.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

Individuals eligible to participate in Part A of this study will meet all the following criteria:

1. Willing and able to provide informed consent after the nature of the study has been explained

2. 18-35 years of age inclusive at Screening (sub cohort A1) or 65-80 years of age inclusive at Screening (sub cohort A2)

3. Willing and able to comply with all study procedures

4. Sub cohort A3 participants must match the age ± 0.5 years and sex of match participant in Part B

5. Participant must be healthy as per the investigator's assessment with no underlying clinically significant diseases (participants with hypertension, diabetes, hypercholesterolemia, and other chronic diseases associated with aging but not thought to interfere with the performance of the mTUG or other study measures may be allowed after consultation with the Medical Monitor)

6. Participant must be able to use the Technology as described in the protocol

7. Have access to a minimum indoor space of 6 meters by 2 meters (or approximately 20 feet by 7 feet) to carry out the mTUG

8. Agree to retain the same level of activity throughout the study and not have plans to stop/start or increase or decrease any exercise programs

9. Have reliable access to working WiFi internet or willingness to use a provided cellular internet connection device

10. Agree to refrain from all alcohol and cannabinoid products within 24 hours prior to performing the mTUG assessment (i.e., three non consecutive days during study Week two, and Weeks two and three of the run in period)

Individuals eligible to participate in Part B of this study must meet all the following criteria:

1. Willing and able to provide informed consent after the nature of the study has been explained

2. Willing and able to comply with all study procedures

3. Have confirmed diagnosis of PD documented in medical records according to UK Brain Bank criteria

4. Confirmed G2019S mutation(s) in the LRRK2 gene either by evidence recorded in medical record with report from accredited laboratory, or through another accredited genetic testing program, or other partner laboratory. Up to 10 participants with homozygous mutations may be enrolled in addition to the 60 participants with heterozygous mutation

5. Hoehn and Yahr Scale Score 1-3

6. Physically and cognitively able to complete protocol specified tasks independently or with some assistance

7. If assistance is required for completion of tasks (e.g., help with the Technology), a caregiver or volunteer must be fully available to assist the participant for the duration of the study

8. Ability to complete the mTUG without the use of a cane or walker and without a personal assistant

9. Ability to complete the mTUG which is not impacted by comorbidities (e.g., participant should not have underlying, clinically significant cardiac or respiratory disease, or musculoskeletal disease). Non-progressive diseases of these organ systems must be approved by the Medical Monitor prior to enrollment; for example, mild to moderate osteoarthritis may be allowable

10. Have access to a minimum indoor space of 6 meters by 2 meters (or approximately 20 feet by 7 feet) to carry out the mTUG

11. A helper or participant is required to be present during the performance of mTUG, if the participant has had more than one fall in the past 12 months

12. The participant's general health status is acceptable for participation in the study (per their physician)

13. Working WiFi internet or willing to use a provided cellular internet connection device

14. Participant must agree to refrain from all alcohol and cannabinoid products within 24 hours prior to performing the mTUG (i.e., three non consecutive days during study Week two, and Weeks two and four of the run in period)

Exclusion Criteria

1. History of mobility, gait, or ambulation problems (defined as mobility limitations that impact walking on a daily basis)

2. History of neurological disease

3. Any elective surgery planned during the study duration, approximately 12-15 months from Screening

4. History of significant head injury within the past 5 years (head injury with loss of consciousness or requiring greater than 24 hours in hospital in relation to head injury)

5. History of alcohol use disorder or other substance abuse disorder (excluding tobacco use), according to the Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-5) in the past 10 years

6. Body Mass Index (BMI) (calculated from self reported height and weight) of greater than 35

7. Pregnant or planning to become pregnant in the next 24 months

8. Has a concurrent disease or condition that, in the view of the investigator, places the subject at high risk of poor treatment compliance or of not completing the study, or would interfere with study participation or would affect safety

1. Any mobility, gait, or ambulation problems other than those related to PD

2. Any deep brain stimulation in situ or planned during the study duration, approximately 12-15 months from Screening

3. Any planned changes in physiotherapy or exercise therapy

4. Planned initiation of, or changes in, cognitive behavioral therapy

5. Any elective planned surgery during the study duration, approximately 12-15 months from Screening

6. History of significant head injury within the past 5 years (head injury with loss of consciousness or requiring greater than 24 hours in hospital in relation to head injury)

7. History of frequent falls (classified as one fall every 1 month)

8. Any other genetic PD causing mutations, for example, a pathogenic GBA mutation

9. History of alcohol use disorder or other substance abuse disorder (excluding tobacco use), according to the DSM-5 in the past 10 years

10. Any other serious concomitant diseases unrelated to PD (e.g., other neurological diseases of any kind, renal failure, liver failure, active cancer)

11. BMI (calculated from self reported height and weight) of greater than 35

12. Pregnant or planning to become pregnant in the next 24 months

13. Has a concurrent disease or condition that, in the view of the investigator, places the subject at high risk of poor treatment compliance or of not completing the study, or would interfere with study participation or would affect safety

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Momentum Pharma

INDUSTRY

Sponsor Role: collaborator

Science 37

INDUSTRY

Sponsor Role: collaborator

Escape Bio, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Carrolee Barlow, MD, PhD

Role: STUDY_CHAIR

Escape Bio, Inc.

Locations

Science 37

Culver City, California, United States

Countries

United States

References

Bright JM, Carlisle HJ, Toda AMA, Murphy M, Molitor TP, Wren P, Andruska KM, Liu E, Barlow C. Differential Inhibition of LRRK2 in Parkinson's Disease Patient Blood by a G2019S Selective LRRK2 Inhibitor. Mov Disord. 2021 Jun;36(6):1362-1371. doi: 10.1002/mds.28490. Epub 2021 Feb 11.

Reference Type: BACKGROUND

PMID: 33836114 (View on PubMed)

Other Identifiers

ESBG2019S-001

Identifier Type: -

Identifier Source: org_study_id