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Alzheimer DiseasePhase 2DOPADNCT03250741

Effects of Dopaminergic Therapy in Patients With Alzheimer's Disease

A Phase 2 study testing Rotigotine transdermal patch in people with Alzheimer Disease, run by I.R.C.C.S. Fondazione Santa Lucia at 1 site in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 50 to 85 years
Conditions the study is for
Alzheimer Disease
What is being tested?
Rotigotine transdermal patch
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
94 participants
Where
1 siteItaly
Study dates
Jun 2016to Nov 2018
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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)
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  • 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

Trial locations and contacts

1 site in 1 country.

Italy1 site

  • Santa Lucia Foundation

    Rome, 00179

Other trials in Italy

About this study

Official title: Effects of Dopaminergic Therapy in Patients With Alzheimer's Disease: a Phase II 24-week, Randomized, Double-blind Placebo Controlled Study.

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.

Read the 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.

Being tested
Rotigotine transdermal patch, Placebo
Keywords
Rotigotine, Dopamine
Medical subject headings
Alzheimer Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Rotigotine transdermal patchDrug

    Also called ROTIGOTINE

    Rotigotine transdermal patches 4mg/24hr

  • PlaceboOther

    Also called Placebo transdermal patch

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

Study groups in NCT03250741
Study groupRoleWhat they receive
Rotigotine 4 mgActive comparatorRotigotine transdermal patches 4 mg
Receives: Drug: Rotigotine transdermal patch
PlaceboPlacebo comparatorPlacebo transdermal patches
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Global cognition

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

    Measured: change from baseline to Week 24

Secondary outcomes (4)

  1. Frontal cognitive functions

    Frontal assessment battery (FAB)

    Measured: change from baseline to Week 24

  2. Activities of daily living

    Alzheimer's disease Cooperative Study - Activities of Daily Living (ADCS-ADL)

    Measured: change from baseline to Week 24

  3. Neurophysiological markers of cortical activity

    TEP amplitude over the PFC

    Measured: change from baseline to Week 24

  4. Neuropsychiatric evaluation

    Neuropsychiatric Inventory (NPI)

    Measured: change from baseline to Week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Aug 2017
  2. Study startJun 2016
  3. Primary completionNov 2018
  4. Study completionNov 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
94 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03250741
Sponsor's protocol ID
EudraCT 2015-002965-43
Acronym
DOPAD
Status last verified
Dec 2018
First submitted
11 Aug 2017
Last updated
17 Dec 2018
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
Individual data sharing
Undecided

Publications

  • 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.

    PubMed 22863599

  • 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.

    PubMed 25309431

  • 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.

    PubMed 24859851

  • 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.

    PubMed 32667654

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Rotigotine transdermal patch in people with Alzheimer Disease, run by I.R.C.C.S. Fondazione Santa Lucia at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Global cognition (time frame: change from baseline to Week 24). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03250741, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2018.

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