A Phase 0 biomarker study in patients with Parkinson*s Disease and healthy controls

Completed

• Conditions: movement disorder; Parkinson's disease; 10028037

• Registration Number: NL-OMON46465
• Lead Sponsor: Denali Therapeutics Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 35

Inclusion Criteria

Groups A and B
1. Confirmed clinical diagnosis of Parkinson*s disease by a qualified neurologist,
2. Hoehn and Yahr stage I-IV, inclusive,
3. Group A: Confirmed mutation in the Leucine-rich repeat kinase 2 (LRRK2) gene of the following types: G2019S, I2020T, R1441G, R1441C, R1441H, N1437H or Y1699C.
4. Group B: Confirmed wild type Leucine-rich repeat kinase 2 (LRRK2) gene.
5. Male or female of 30-85 years of age at screening (inclusive). Group A patients may be as young as 25 years of age with Investigatory and Sponsor agreement.
6. Body mass index (BMI) between 18 and 35 kg/m2 (inclusive), and with a minimum weight of 50 kg at screening.
7. Able to speak, read, and understand study procedures in Dutch sufficiently to allow completion of all study assessments.
8. Mentally competent as assessed by the screening physician and *if deemed necessary- by the treating neurologist
9. Must understand and provide written informed consent prior to the initiation of any protocol-specific procedures.
10. Willing and able to maintain stable doses and regimens for all medications, herbal treatments, medical marijuana, dietary supplements and caffeine intake from the screening visit through the last study visit.
11. Willing and able to abstain from alcohol 48 hours prior to all study procedures at study visits 1 and 2.;Group C:
1. No clinical evidence or history of Parkinson disease
2. Male or female matched to a participant in Group A and/or Group B for gender, race, age (+/- 5 years) and BMI (+/- 3.5, with a minimum weight of 50 kg at screening).
3. Able to speak, read, and understand study procedures in Dutch sufficiently to allow completion of all study assessments.
4. Must understand and provide written informed consent prior to the initiation of any protocol-specific procedures.
5. Willing and able to maintain stable doses and regimens for all medications, herbal treatments, dietary supplements and caffeine intake from the screening visit through the last study visit.
6. Willing and able to abstain from alcohol 48 hours prior to all study procedures at study visits 1 and 2.

Exclusion Criteria

Groups A * C
1. Self-reported substance or alcohol dependence (excluding caffeine), and/or participated in a substance or alcohol rehabilitation program to treat substance or alcohol dependence within the past 6 months
2. History or presence of clinically significant or unstable abnormality as assessed by physical examination, medical history, 12-lead ECG, vital signs, or laboratory values, which in the opinion of the investigator would jeopardize the safety of the participant or the validity of the study results
3. Positive urine drug screen, except for medical marijuana which is permitted
4. Positive breath alcohol test. Participants with a positive result may be rescheduled at the investigator*s discretion
5. Groups A and B: Parkinson disease associated mutations in the GBA gene, as determined by genetic testing or documented before screening.
6. Group C only: first order relative with Parkinson disease
7. Females who have a positive serum or urine pregnancy test
8. Positive Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab) at screening
9. Hemoglobin level <7.0 mmol/L (males) or <6.0 mmol/L (females)
10. Donation or loss of more than 500 mL whole blood within 30 days preceding entry into the treatment period
11. Difficulty with venous access or unsuitable or unwilling to undergo catheter insertion
12. History of clinically significant back pathology and/or back injury (e.g. degenerative disease, spinal deformity or spinal surgery) that may predispose to complications or technical difficulty with lumbar puncture
13. Significant coagulation abnormality (e.g. hemophilia, platelet count <100,000/microliter or clinically significant elevation in PT or PTT at screening), or has a medical condition requiring treatment with an anticoagulant (e.g. warfarin) or with two or more antiplatelet agents
14. Treatment with an investigational drug within 5 times the elimination half-life or within 30 days (whichever is longer) prior to Visit 1, or is currently enrolled in any research judged not to be scientifically or medically compatible with this study
15. Hospitalization during the 6 weeks prior to Visit 1
16. An employee of the sponsor or research site personnel directly affiliated with this study or their immediate family members defined as a spouse, parent, child or sibling, whether biological or legally adopted
17. Anyone who, in the opinion of the investigator or designee, is not considered to be suitable and is unlikely to comply with the study protocol for any reason
18. Current smoker or tobacco use within 6 months
19. Groups B and C only: presence of Type 2 diabetes based on medical history or screening laboratories, unless matched to a patient from Group A with Type 2 diabetes

Study & Design

• Study Type: Observational invasive
• Study Design: Not specified