Effects of Dopaminergic Therapy in Patients With Alzheimer's Disease

NCT03250741 | Completed Phase 2

• 1 other identifier: EudraCT 2015-002965-43
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 1

Brief Summary

This is phase IIa 24-week, prospective, randomized, double-blind placebo controlled study. The study is designed to evaluate the efficacy, safety, and tolerability of transdermal patch of Rotigotine (RTG) versus placebo (PLC) as add-on therapy with AChEI in patients with mild AD according to the consensus diagnostic criteria and MMSE score of ≥18 and ≤24 at screening. Two groups of patients with mild AD will be involved (50 patients each). One group will be assigned to treatment with RTG 4 mg and the other one to PLC as add on to AChEI therapy (Rivastigmine). Clinical and neurophysiological measurements will be collected before and after drug administration.

Conditions

Alzheimer Disease

Keywords

Rotigotine; Dopamine

Outcome Measures

Primary Outcomes (1)

• Global cognition

  Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog)

  change from baseline to Week 24

Secondary Outcomes (4)

• Frontal cognitive functions

  change from baseline to Week 24

• Activities of daily living

  change from baseline to Week 24

• Neurophysiological markers of cortical activity

  change from baseline to Week 24

• Neuropsychiatric evaluation

  change from baseline to Week 24

Study Arms (2)

Rotigotine 4 mg

ACTIVE COMPARATOR

Rotigotine transdermal patches 4 mg

Drug: Rotigotine transdermal patch

Placebo

PLACEBO COMPARATOR

Placebo transdermal patches

Other: Placebo

Interventions

Rotigotine transdermal patch DRUG

Rotigotine transdermal patches 4mg/24hr

Also known as: ROTIGOTINE

Rotigotine 4 mg

Placebo OTHER

Placebo transdermal patches of the same size as for Rotigotine transdermal patches

Also known as: Placebo transdermal patch

Placebo

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient (or if applicable the legally acceptable representative if different from the responsible caregiver) and the responsible caregiver have signed the Informed Consent Form.
• The patient has probable AD, diagnosed according to National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria.
• The patient is a man or woman, aged ≤ 85 years.
• The patient has a Clinical Dementia Rating (CDR) total score of 0.5 or 1 (mild) and MMSE score of 20-26 (inclusive) at Screening.
• Has at least one identified adult caregiver who is able to provide meaningful assessment of changes in subject behavior and function over time and provide information on safety and tolerability, and is able to verify daily compliance with study drug
• The patient has been treated with acetylcholinesterase inhibitor (AChEI), i.e., donepezil, galantamine, or rivastigmine, at the time of Screening
• For at least 3 months
• The current dosage regimen and must have remained stable for ≥ 8 weeks
• It must be planned that the dosage regimen will remain stable throughout participation in the study

You may not qualify if:

• Significant neurodegenerative disorder of the central nervous system other than Alzheimer's disease, e.g., Lewy body dementia, Parkinson's disease, multiple sclerosis, progressive supranuclear palsy, hydrocephalus, Huntington's disease, any condition directly or indirectly caused by Transmissible Spongiform Encephalopathy (TSE), Creutzfeldt-Jakob Disease (CJD), variant Creutzfeldt-Jakob Disease (vCJD), or new variant Creutzfeldt-Jakob Disease (nvCJD)
• The patients has history of seizure (with the exception of febrile seizures in childhood)
• Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition - Text Revision (DSM IV-TR) criteria met for any of the following within specified period:
• Major depressive disorder (current)
• Schizophrenia (lifetime)
• Other psychotic disorders, bipolar disorder, or substance (including alcohol) related disorders (within the past 5 years)
• Metal implants in the head (except dental), pacemaker, cochlear implants, or any other non-removable items that are contraindications to MR imaging.
• Evidence of clinically significant disease including but not limited to pulmonary, gastrointestinal, renal, hepatic, endocrine, cardiovascular or metabolic disorder (Patients with controlled diabetes, or hypertension, or complete/partial right bundle branch block may be included in the study).
• Treatment currently or within 6 months before Baseline with any of the following medications:
• Typical and atypical antipsychotics (i.e. Clozapine, Olanzapine)
• Antiparkinson agents (e.g., levodopa, dopamine agonists, COMT inhibitors, amantadine, monoamine oxidase B inhibitors, anticholinergics etc)
• Carbamazepine, Primidone, Pregabalin, Gabapentin
• Memantine

Sponsors & Collaborators

• I.R.C.C.S. Fondazione Santa Lucia: lead

Study Sites (1)

Santa Lucia Foundation

Rome, 00179, Italy

Location

Related Publications (4)

• Martorana A, Di Lorenzo F, Esposito Z, Lo Giudice T, Bernardi G, Caltagirone C, Koch G. Dopamine D(2)-agonist rotigotine effects on cortical excitability and central cholinergic transmission in Alzheimer's disease patients. Neuropharmacology. 2013 Jan;64:108-13. doi: 10.1016/j.neuropharm.2012.07.015. Epub 2012 Aug 1.

  PMID: 22863599 BACKGROUND

• Martorana A, Koch G. "Is dopamine involved in Alzheimer's disease?". Front Aging Neurosci. 2014 Sep 25;6:252. doi: 10.3389/fnagi.2014.00252. eCollection 2014.

  PMID: 25309431 RESULT

• Koch G, Di Lorenzo F, Bonni S, Giacobbe V, Bozzali M, Caltagirone C, Martorana A. Dopaminergic modulation of cortical plasticity in Alzheimer's disease patients. Neuropsychopharmacology. 2014 Oct;39(11):2654-61. doi: 10.1038/npp.2014.119. Epub 2014 May 26.

  PMID: 24859851 RESULT

• Koch G, Motta C, Bonni S, Pellicciari MC, Picazio S, Casula EP, Maiella M, Di Lorenzo F, Ponzo V, Ferrari C, Scaricamazza E, Caltagirone C, Martorana A. Effect of Rotigotine vs Placebo on Cognitive Functions Among Patients With Mild to Moderate Alzheimer Disease: A Randomized Clinical Trial. JAMA Netw Open. 2020 Jul 1;3(7):e2010372. doi: 10.1001/jamanetworkopen.2020.10372.

  PMID: 32667654 DERIVED

MeSH Terms

Conditions

Alzheimer Disease

Interventions

rotigotine

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Alessandro Martorana, MD, PhD

  University of Rome Tor Vergata

  STUDY DIRECTOR

• Giacomo Koch, MD, PhD

  Santa Lucia Foundation IRCCS

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PI

Study Record Dates

• First Submitted: August 11, 2017
• First Posted: August 16, 2017
• Study Start: June 1, 2016
• Primary Completion: November 1, 2018
• Study Completion: November 1, 2018
• Last Updated: December 17, 2018

Record last verified: 2018-12

Locations

IT (1)