Phase 0 biomarker assessment of day-to-day, within-day and interindividual variability in GBA pathway biomarkers in healthy adults and patients with Parkinson*s disease with and without heterozygous GBA1-mutations

Completed

• Conditions: Parkinsons disease; Parkinsons disease with and without GBA mutation; 10028037

• Registration Number: NL-OMON52359
• Lead Sponsor: BIAL R&D INVESTMENTS, S.A

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: 48

Inclusion Criteria

Cohort A
Group 1 (healthy volunteers)
1. Male or female 18 * 55 years of age at screening (inclusive)
2. BMI in the range of 18 * 32 kg/m2.

Cohort B
Group 1 (healthy volunteers)
1. Male or female 18 * 65 years of age at screening (inclusive)
2. BMI in the range of 18 * 32 kg/m2.

Cohort A and B

Group 2 and 3 (PD-GBA+ and PD-GBA-)
3. Confirmed clinical diagnosis of Parkinson disease by a qualified neurologist.
4. Hoehn and Yahr stage I-IV, inclusive
5. Male or female of 30-85 years of age at screening (inclusive)
6. BMI in the range of 18 * 32 kg/m2.
7. PD-GBA+ group (2): confirmed presence of GBA1 mutation via (historic)
genotyping
8. PD-GBA- group (3): confirmed absence of GBA1 mutation via (historic)
genotyping
Groups 1, 2 and 3
9. Able to speak, read, and understand study procedures in Dutch sufficiently
to allow completion of all study assessments.
10. Must understand and provide written informed consent prior to the
initiation of any protocol-specific procedures.
11. 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.
12. Willing and able to abstain from alcohol 24 hours prior to all study
procedures at study visits 1, 2 and 3.
13. Women of childbearing potential must use a form of birth control (e.g. oral
contraceptive, condom use, IUD, abstinence of hetero-sexual intercourse)

Exclusion Criteria

Group 1 and 2 and 3
1. Significant haematological abnormalities during screening such as anaemia,
leukopenia, (haemoglobin level <7.0 mmol/L (males) or <6.0 mmol/L (females)),
or any other significant abnormalities in clinical laboratory test values.
2. Recent participation (<90 days / 5x T1/2) in an interventional study for
Parkinson disease
3. Any other clinically significant neuro-degenerative disorder
4. Recent blood loss or blood donation (>500mL whole blood) in the past 30 days.
5. Recent infection with hospital admission (<1 month)
6. Alcohol or drugs abuse in the past 12 months
7. Have no clinical or electrocardiographic signs of ischemic heart disease as
determined by the Investigator with normal cardiac intervals appropriate for
their gender. The Screening 12 lead ECG conduction intervals must be within
gender specific normal range (e.g., QTcf female *470 msec QTcF males *450 msec,
PR interval *220 msec).
8. Vital sign measurements must be within the following ranges during
screening:
a. body temperature, >35C to *38C
b. systolic blood pressure, >90 to *160 mm Hg
c. diastolic blood pressure, >40 to *95 mm Hg
d. pulse rate, >40 to *100 bpm
9. Positive serology for human immunodeficiency virus (HIV), hepatitis B virus
(HBV) (positive hepatitis B core antibody [anti-HBc] with negative hepatitis B
DNA is acceptable), or hepatitis C virus (HCV) (treated/resolved hepatitis C
with negative polymerase chain reaction [PCR] RNA is allowed)
10. Any other issue that, in the opinion of the investigator, would make the
participant ineligible for study participation

Group 1
11. Clinical evidence or history of Parkinson disease, parkinsonism or Gaucher
disease
12. First order relative with Parkinson disease or Gaucher disease
13. Any historyof unstable or poorly controlled psychiatric, endocrine,
pulmonary, cardiovascular, gastrointestinal, hepatic, pancreatic, renal,
metabolic, hematologic, immunologic, or allergic disease, or other major
disorders. Well-controlled conditions are permitted if investigator and Sponsor
agree.

Study & Design

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

Primary Outcome Measures

Name	Time	Method
<p>Day-to-day variability (%CV) of:<br /><br>* Glucocerebrosidase and galactocerebrosidase activity (in Dried blood spots)<br /><br>* Acid ceramidase activity (in PBMCs)<br /><br>* Glucosylsphingosine concentration (in granulocytes)<br /><br>* Ceramide and dihydroceramide concentrations (in lymphocytes)</p><br>