Trials Sponsors Conditions Drugs Pricing

Brief Summary

REM Behavior Sleep Disorder (RBD) is a sleep disorder causing people to 'act out' their dreams. A high percentage of individuals with idiopathic RBD (iRBD) are known to develop conditions affecting the neurons in the brain such as Parkinson's disease (PD). Based on the increased risk to develop PD, individuals with iRBD are currently considered ideal candidates for therapies that can possibly protects brain cells, due to the critical window of opportunity to intervene early before brain cell loss progresses significantly. Early changes of PD are associated with a number of symptoms including loss of smell, constipation, anxiety and depression. In addition, early heart and brain abnormalities can be visualized using specialized imaging techniques called 123I-MIBG myocardial scintigraphy (MIBG) and dopamine transporter (DAT) single photon emission computerized tomography (SPECT) respectively. The combined presence of certain symptoms and the use of these imaging techniques are considered early markers of PD in individuals with iRBD. In other conditions, like heart failure, MIBG abnormalities are reversed by drugs able to block excessive adrenergic stimulation, known as beta-blockers. In this study the investigators want to learn about the effect of treatment with the beta-blocker carvedilol on MIBG abnormalities found in iRBD patients at risk to develop PD. The investigators believe that reversing the MIBG abnormality might prelude to a slowing of the neurodegenerative process. This drug is approved by the U.S. Food and Drug Administration (FDA) for congestive heart failure, hypertension and left ventricular dysfunction after myocardial infarction. However, carvedilol is not approved by the FDA in patients with iRBD at risk for PD. The available doses for this drug oral formulations are 3.125mg, 6.25mg, 12.5mg and 25mg. Changes visualized with the MIBG imaging technique will be correlated to the presence and severity of neurological (i.e. tremors, stiffness, slow movements, walking difficulties) and other symptoms associated with PD (i.e. abnormal smell, constipation, depression, color vision abnormalities), as measured by specific clinical scales and exams.

Conditions

Pre-motor Parkinson Disease REM Sleep Behavior Disorder Symptomatic Parkinson Disease

Keywords

Early Parkinson DiseaseREM Sleep Behaviour Disorder (RBD)carvedilolAutonomic dysfunctionNeurodegeneration

Outcome Measures

Primary Outcomes (1)

123I-MIBG reuptake changes
123I-MIBG reuptake will be measured by early and late Heart to Mediastinal ratio (H/M) and Washout ratio (WR) which will be calculated using the following formula: \[(early heart counts/pixel - early mediastinum counts/pixel) - (late heart counts/pixel decay-corrected - late mediastinum counts/pixel decay-corrected)\]/(early heart counts/pixel - early mediastinum counts/pixel). Care will be taken to exclude lung or liver from the myocardial and large vessels and lung from the mediastinum region of interest. MIBG abnormality cutoffs will be set for values of late H/M \<2.2 and WR \>30%.
At baseline and at 26 weeks of treatment.

Secondary Outcomes (2)

Adverse Events frequency
every 3 months up to 34 weeks

Study Arms (1)

carvedilol therapy

EXPERIMENTAL

The dosage of carvedilol will be gradually increased from the initial recommended starting dose of 3.125 mg twice/daily, the target dose will be 25mg twice daily (50 mg/day) and participants will take 50 mg/day carvedilol for 6 months.Subjects that cannot tolerate the 50 mg daily dose, will be offered to continue at the 25 mg daily dose.

Drug: Carvedilol

Interventions

CarvedilolDrug

At the end of Baseline visit, carvedilol 3.125 twice daily will be initiated and maintained for 1 week, increased to 6.25twice daily (dispensed at week 1visit), to 12.5mg twice daily (dispensed at week 2) and a max dose of 25mg twice daily (dispensed at week 4 visit), as tolerated. A subject that cannot tolerate at least a 25 mg daily dose will be excluded from the study. Subjects that cannot tolerate the 50 mg daily dose, will be offered to continue at the 25 mg daily dose. The project will include a washout period at study end.

Also known as: Coreg

carvedilol therapy

Registry-reported names are shown in full. Names without a link have not yet been matched to a Syfrah profile.

Eligibility Criteria

Age50 Years - 85 Years

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

Male or female of age between 50 and 85 years at time of enrollment.
Diagnosis of idiopathic REM sleep behavior disorder (iRBD) or Diagnosis of hyposmia. Diagnosis of RBD will be, established either as 'definite RBD' according to the criteria proposed by the International Classification of Sleep Disorders (ICSD)-2 \[AASM, 2005\] or 'probable RBD' following a score of 6 or higher in the RBD questionnaire (RBDSQ) with a score of at least 1 in subitems 6.1 to 6.4 of question 6.

Sponsors & Collaborators

Michele Tagliati, MD
Otherlead

Study Sites (1)

Michele L Lima Gregorio

Los Angeles, California, 90046, United States

Related Publications (59)

Amino T, Orimo S, Itoh Y, Takahashi A, Uchihara T, Mizusawa H. Profound cardiac sympathetic denervation occurs in Parkinson disease. Brain Pathol. 2005 Jan;15(1):29-34. doi: 10.1111/j.1750-3639.2005.tb00097.x.
PMID: 15779234BACKGROUND
Boeve BF. REM sleep behavior disorder: Updated review of the core features, the REM sleep behavior disorder-neurodegenerative disease association, evolving concepts, controversies, and future directions. Ann N Y Acad Sci. 2010 Jan;1184:15-54. doi: 10.1111/j.1749-6632.2009.05115.x.
PMID: 20146689BACKGROUND

MeSH Terms

Conditions

REM Sleep Behavior DisorderParkinson Disease, SecondaryParkinson DiseasePrimary DysautonomiasNerve Degeneration

Interventions

Carvedilol

Condition Hierarchy (Ancestors)

REM Sleep ParasomniasParasomniasSleep Wake DisordersNervous System DiseasesMental DisordersParkinsonian DisordersBasal Ganglia DiseasesBrain Diseases

Study Officials

Michele Tagliati, MD, FAAN
Cedars-Sinai Medical Center
PRINCIPAL INVESTIGATOR

Study Design

Study Type: interventional
Phase: phase 2
Allocation: NA
Masking: NONE
Purpose: TREATMENT
Intervention Model: SINGLE GROUP
Sponsor Type: OTHER
Responsible Party: SPONSOR INVESTIGATOR
PI Title: Professor and Vice Chairman, Director of Movement Disorders

Study Record Dates

First Submitted

December 9, 2018

First Posted

December 13, 2018

Study Start

Adrenergic Blockers for Cardiac Changes in Early Parkinson's Disease (Protocol 53136)

Brief Summary

Registry Overview

Trial Relationships

Study Timeline

First Submitted

First Posted

Study Start

Primary Completion

Study Completion

Conditions

Keywords

Outcome Measures

Primary Outcomes (1)

Secondary Outcomes (2)

Study Arms (1)

carvedilol therapy

Interventions

Eligibility Criteria

You may qualify if:

Sponsors & Collaborators

Study Sites (1)

Related Publications (59)

MeSH Terms

Conditions

Interventions

Condition Hierarchy (Ancestors)

Study Officials

Study Design

Study Record Dates

Other Outcomes (10)

You may not qualify if:

Intervention Hierarchy (Ancestors)

Data Sharing

Source record

Locations

Adrenergic Blockers for Cardiac Changes in Early Parkinson's Disease (Protocol 53136)

Brief Summary

Registry Overview

Trial Relationships

Related Scientific Literature

Study Timeline

First Submitted

First Posted

Study Start

Primary Completion

Study Completion

Conditions

Keywords

Outcome Measures

Primary Outcomes (1)

Secondary Outcomes (2)

Study Arms (1)

carvedilol therapy

Interventions

Eligibility Criteria

You may qualify if:

Sponsors & Collaborators

Study Sites (1)

Related Publications (59)

MeSH Terms

Conditions

Interventions

Condition Hierarchy (Ancestors)

Study Officials

Study Design

Study Record Dates

Other Outcomes (10)

You may not qualify if:

Intervention Hierarchy (Ancestors)

Data Sharing

Source record

Locations