Parkinson's Disease With Mild Cognitive Impairment Treated With Nicotinic Agonist Drug

NCT ID: NCT04810104

Last Updated: 2022-10-14

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-31
• Study Completion Date: 2024-04-30

Brief Summary

To test for the first time the potential of a nicotinic agonist on cognitive symptoms in people with mild cognitive impairment (MCI) in Parkinson's disease (PD), referred to as PD-MCI.

Detailed Description

There is an unmet clinical need to treat PD-MCI. As outlined previously, PD-MCI is common, has important clinical consequences, and there is currently no available treatment. Moreover, the underlying pathology of cognitive impairment in PD indicates that nicotinic agonists may be particularly relevant for this condition. This is a randomised, double-blind, placebo-controlled, parallel-group, phase 2a study of AZD0328, a selective α7 nicotinic receptor agonist, in PD-MCI. The study is an international, multi-centre study, which will take place across sites in Europe.

PD-MIND will for the first time test the potential of a nicotinic agonist on cognition in PD-MCI. The primary outcome is attention, as it is a key cognitive domain in the PD-MCI profile and most likely to be affected by a α7 nicotinic agonist. Exploratory outcome measures will guide decisions on the design and conduct of future larger Phase 3 trials. Qualifying participants will be randomly assigned at baseline to either receive 0.5mg twice a day (bis in die, BID) of AZD0328 or placebo for 12 weeks. A total of 160 participants with PD-MCI will be enrolled to the study: 80 in the active (AZD0328) group and 80 in the control (placebo) group. Participants will undertake face-to-face assessments at screening, baseline, and then 3- 6- and 12- weeks after beginning study treatment (see Figure 2 for trial design overview). A subset of 90 participants will also undergo an MRI biomarker component prior to study drug administration and at study end.

Conditions

Parkinson Disease; Mild Cognitive Impairment

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Active drug: AZD0328

Participants will receive AZD0328 capsules for oral administration.AZD0328 is a selective α7 nicotinic receptor agonist, The total daily dosage of AZD0328 is 1mg per day; administered as 0.5mg twice daily / BID. The study treatment period is 12-weeks.

Group Type: EXPERIMENTAL

AZD0328

Intervention Type: DRUG

Active study drug

Placebo

Participants will receive identical-appearing placebo capsules for oral administration.Participants will be instructed to take 2 capsules in the morning and 2 capsules in the evening for a 12-week period.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Non-active study drug

Interventions

AZD0328

Active study drug

Intervention Type: DRUG

Placebo

Non-active study drug

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Aged between 50 to 80 years (inclusive) at time of consent
• Duration of motor symptoms of at least 1 year
• Hoehn and Yahr stage between 1 and 3 (inclusive) in ON state
• Diagnosis of PD according to United Kingdom (UK) Brain Bank criteria
• Score on Clinical Dementia Rating (CDR) scale = 0.5
• Diagnosis of PD-MCI according to MDS PD-MCI, Level I criteria
• Duration of cognitive impairment of at least 3 months (to distinguish from mild delirium)

Exclusion Criteria

• Insufficient fluency in English or local language to complete assessments
• Severe visual or auditory impairment that may interfere with participant's ability to complete assessments
• Unable to provide informed consent at screening visit
• Participation in a clinical study involving an investigational drug within 4 months prior to screening
• Smoking (cigarettes, pipes, cigars, e-cigarettes etc.) or use of smokeless tobacco products (chewing / dipping tobacco, snuff etc.) or anti-smoking nicotine containing products (patches/gum/sprays etc.), within the last 12 weeks
• HADS depression subscale score ≥ 11
• History of deep brain stimulation or other neurosurgical procedure
• Diagnosis of dementia, including Parkinson's disease dementia (PDD) or Dementia with Lewy Bodies (DLB).
• Diagnosis of schizophrenia, bipolar disorder or other psychotic disorder
• Malignant neoplasms within 3 years of screening (except for basal or squamous cell carcinoma of the skin); or had curative surgery/treatment and has been free of malignancy for at least 12 months)
• Any medical condition that in the opinion of the investigator may be contributing to cognitive impairment, above and beyond that caused by the participant's PD,
• Current evidence of any other medical condition not stably or adequately controlled, and which in the opinion of the investigator may affect participant safety or study participation
• Using any prohibited medications or permitted medications that do not meet stable dosing regimen requirements, as specified in section 5.7
• Clinically significant vital sign or ECG measure at screening or baseline visit, that in the opinion of the investigator would prevent participant from safely participating in this study
• Clinically significant clinical laboratory result from screening visit, that in the opinion of the investigator would prevent participant from safely participating in this study
• Significant renal function impairment as indicated by estimated glomerular filtration rate (eGFR) < 45ml/min); Note: The eGFR is calculated using a formula derived from the Modification of Diet in Renal Disease Study (MDRD formula): eGFR= [186.3 x (Creatinine/88.4)-1.154 x (Age)-0.203] x [0.742 if female] x [1.210 if black]
• Unable to complete computerised cognitive test battery
• Marked cerebrovascular disease from MRI or CT scan within last 12 months (defined as Fazekas scale ≥ grade 3)
• Females who are breast-feeding
• Female participants assessed as being of child-bearing potential that have a positive pregnancy test at screening or baseline
• The participant does not understand or agree to comply with the contraception or reproductive requirements of the study

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Helse Stavanger HF

OTHER_GOV

Sponsor Role: collaborator

Michael J. Fox Foundation for Parkinson's Research

OTHER

Sponsor Role: collaborator

Parkinson's UK

OTHER

Sponsor Role: collaborator

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

Masaryk University

OTHER

Sponsor Role: collaborator

Norges Parkinsonforbund, Norway

UNKNOWN

Sponsor Role: collaborator

University of Exeter

OTHER

Sponsor Role: collaborator

Stichting Lygature

UNKNOWN

Sponsor Role: collaborator

Innovative Medicines Initiative

OTHER

Sponsor Role: collaborator

King's College London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dag Aarsland, PhD

Role: STUDY_DIRECTOR

King's College London; Stavager Univeristy Hospital

Other Identifiers

2019-002423-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PD-MIND

Identifier Type: -

Identifier Source: org_study_id