Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Effects of Dopaminergic Therapy in Patients With Alzheimer's Disease (DOPAD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03250741
Recruitment Status : Completed
First Posted : August 16, 2017
Last Update Posted : December 17, 2018
Sponsor:
Information provided by (Responsible Party):
Giacomo Koch, I.R.C.C.S. Fondazione Santa Lucia

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.

Condition or disease Intervention/treatment Phase
Alzheimer Disease Drug: Rotigotine transdermal patch Other: Placebo Phase 2

Detailed Description:

The current study has the ambition to provide first time evidence that dopaminergic stimulation may have a clinical impact in patients with mild AD.

Cognitive Assessment: Before and after the 24 weeks of treatment the ADAS-Cog, ADCS-ADL and the Frontal assessment battery (FAB) will be administered. FAB will be performed to measure changes in frontal executive functions (Apollonio et al, 2005) .

Neurophysiological investigations will be performed to identify quantifiable biomarkers underlying the effects induced by dopamine agonist on the neurodegenerative brain. The application of recent neurophysiological tools, such as the combined use of transcranial magnetic stimulation (TMS) during electroencephalography (EEG) will allow to measure how dopamine agonists are able to modulate the cortical activity of the prefrontal cortex in AD patients (Kähkönen et al., 2005; Julkunen et al., 2008), likely trough DA terminals originating from the ventral tegmental nucleus, defining the neurophysiological biomarkers of clinical improvement For EEG-TMS recordings, a TMS-compatible EEG equipment will be used for recording EEG activity from the scalp (BrainAmp 32MRplus, BrainProducts). The EEG will be continuously acquired from 64 scalp sites positioned according to the 10-20 International System. To precisely position the coil over the cortical sites across different sessions, a neuronavigation system (Softaxic, E.M.S.) will be used. Neurophysiological changes induced by dopamine-agonist will be indexed by the following measures: corticospinal excitability, cortical reactivity, connectivity and plasticity. Specifically, the cortical reactivity and cortico-cortical connectivity will be evaluated respectively over the prefrontal cortex and between connected areas. We will employ TMS-evoked cortical responses (i.e., TEPs) as a novel probe of dopamine-agonist induced cortical excitability changes (Ilmoniemi et al., 1997; Komssi and Kahkonen, 2006; Julkunen et al., 2008; Miniussi and Thut, 2009; Miniussi et al., 2012; Premoli et al., 2014). To reach this aim, TEPs will serve as markers of left prefrontal cortex (PFC) reactivity whereas the spreading of their cortical activation will serve as an index of connectivity between targeted cortex and functionally connected areas underlying frontal cognitive network.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 94 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of Dopaminergic Therapy in Patients With Alzheimer's Disease: a Phase II 24-week, Randomized, Double-blind Placebo Controlled Study.
Actual Study Start Date : June 2016
Actual Primary Completion Date : November 2018
Actual Study Completion Date : November 2018


Arm Intervention/treatment
Active Comparator: Rotigotine 4 mg
Rotigotine transdermal patches 4 mg
Drug: Rotigotine transdermal patch
Rotigotine transdermal patches 4mg/24hr
Other Name: ROTIGOTINE

Placebo Comparator: Placebo
Placebo transdermal patches
Other: Placebo
Placebo transdermal patches of the same size as for Rotigotine transdermal patches
Other Name: Placebo transdermal patch




Primary Outcome Measures :
  1. Global cognition [ Time Frame: change from baseline to Week 24 ]
    Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog)


Secondary Outcome Measures :
  1. Frontal cognitive functions [ Time Frame: change from baseline to Week 24 ]
    Frontal assessment battery (FAB)

  2. Activities of daily living [ Time Frame: change from baseline to Week 24 ]
    Alzheimer's disease Cooperative Study - Activities of Daily Living (ADCS-ADL)

  3. Neurophysiological markers of cortical activity [ Time Frame: change from baseline to Week 24 ]
    TEP amplitude over the PFC

  4. Neuropsychiatric evaluation [ Time Frame: change from baseline to Week 24 ]
    Neuropsychiatric Inventory (NPI)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   50 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.
  2. 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.
  3. The patient is a man or woman, aged ≤ 85 years.
  4. 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.
  5. 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
  6. 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

Exclusion Criteria:

  1. 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)
  2. The patients has history of seizure (with the exception of febrile seizures in childhood)
  3. 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)
  4. Metal implants in the head (except dental), pacemaker, cochlear implants, or any other non-removable items that are contraindications to MR imaging.
  5. 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).
  6. 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03250741


Locations
Layout table for location information
Italy
Santa Lucia Foundation
Rome, Italy, 00179
Sponsors and Collaborators
I.R.C.C.S. Fondazione Santa Lucia
Investigators
Layout table for investigator information
Study Director: Alessandro Martorana, MD, PhD University of Rome Tor Vergata
Principal Investigator: Giacomo Koch, MD, PhD Santa Lucia Foundation IRCCS
Publications of Results:
Other Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Giacomo Koch, PI, I.R.C.C.S. Fondazione Santa Lucia
ClinicalTrials.gov Identifier: NCT03250741    
Other Study ID Numbers: EudraCT 2015-002965-43
First Posted: August 16, 2017    Key Record Dates
Last Update Posted: December 17, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Giacomo Koch, I.R.C.C.S. Fondazione Santa Lucia:
Rotigotine
Dopamine
Additional relevant MeSH terms:
Layout table for MeSH terms
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Rotigotine
Dopamine Agonists
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs