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Terazosin Effect on Cardiac Changes in Early Parkinson's Disease

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ClinicalTrials.gov Identifier: NCT04386317
Recruitment Status : Recruiting
First Posted : May 13, 2020
Last Update Posted : August 26, 2022
Sponsor:
Information provided by (Responsible Party):
Michele Tagliati, MD, Cedars-Sinai Medical Center

Study Description
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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 this study the investigators want to learn about the effect of treatment with the beta-blocker terazosin 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 Benign Prostatic Hyperplasia (BPH) and Hypertension. However, terazosin is not approved by the FDA in patients with iRBD at risk for PD. The available doses for this drug oral formulations are 1mg, 2 mg, 5mg and 10 mg.

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.


Condition or disease Intervention/treatment Phase
REM Sleep Behavior Disorder Pre-motor Parkinson's Disease Symptomatic Parkinson Disease Drug: Terazosin Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Effect of a1- Adrenergic Receptor Antagonist Therapy on Cardiac and Striatal Transporter Uptake in Pre-Motor and Symptomatic Parkinson's Disease
Actual Study Start Date : November 1, 2020
Estimated Primary Completion Date : December 30, 2025
Estimated Study Completion Date : December 30, 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: terazosin therapy Drug: Terazosin
Fifteen patients with defined pre-motor PD risk and abnormal baseline 123I-MIBG uptake, with or without 123I-Ioflupane uptake abnormality or PD motor symptoms, will be recruited to receive daily oral doses of terazosin 5 mg or 10 mg. The dosage of terazosin will be gradually increased from the initial recommended starting dose of 1 mg daily at bedtime and titrated stepwise to 2mg, 5mg or 10 mg weekly, according to patient tolerability, as measured by subjective complaints, arterial blood pressure and heart rate. The target dose will be 5 mg or 10 mg daily based on subject's tolerability. Development of incompatibility will be addressed by individually adjusting the dose of terazosin.


Outcome Measures
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Primary Outcome Measures :
  1. Differences in 123I-MIBG reuptake, as measured by early and late Heart to mediastinum (H/M) ratio, and Washout Ration (WR), at 26 weeks of treatment with the adrenergic blocker terazosin [ Time Frame: 26 weeks after medication titration ]

Secondary Outcome Measures :
  1. Incidence of adverse events [ Time Frame: 26 weeks after medication titration ]
    Safety will be monitored collecting the type and frequency of adverse events, including clinical symptoms

  2. Heart Rate variability changes from baseline at 26 weeks after study medication titration [ Time Frame: 26 weeks after medication titration ]
  3. Incidence of abnormal vital signs [ Time Frame: 26 weeks after medication titration ]
    Changes in vital signs ( Blood pressure and Heart rate)


Eligibility Criteria
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Ages Eligible for Study:   25 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female of age between 25 and 85 years at time of enrollment.
  • Diagnosis of idiopathic REM sleep behavior disorder (iRBD), 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) [Nomura et al, 2011], with a score of at least 1 in subitems 6.1 to 6.4 of question 6 [Halsband et al, 2018].

  • At least one of the following:

    1. Diagnosis of hyposmia, established as a University of Pennsylvania Smell Identification Test (UPSIT) score < 20th percentile for the individual's age group and sex.
    2. Functional constipation assessed by a scores > 4 on a questionnaire based on modified ROME IV diagnostic criteria.
    3. Color vision abnormality, as assessed using HRR Pseudoisochromatic Plates, in the absence of congenital dyschromatopsia
    4. Symptoms of depression, as assessed by a Beck Depression Inventory (BDI) fast screen score >3 or concurrent use of antidepressant medications.
  • Abnormal 123I-MIBG myocardial scintigraphy, as defined by a Late H/M ratio < 2.2 and/or a WR >20%, with normal cardiac ejection fraction (LVEF >55%).
  • Capacity to give informed consent

Exclusion Criteria:

  • Secondary Parkinsonism, including tardive
  • Concurrent dementia defined by a score lower than 22 on the MOCA
  • Concurrent severe depression defined by a BDI fast screen score greater than 13

  • Comorbidites related to SNS hyperactivity

    • Heart failure (LVEF< 45%)
    • Recent myocardial revascularization (< 12 weeks)
    • Hypertension (SBP >150 mmHg or DBP> 100mmHg)
    • Chronic Atrial fibrillation
    • Concurrent use of Alpha- adrenergic antagonist
    • Diabetes mellitus
    • COPD
    • Untreated Severe Sleep Apnea; Apnea-Hypopnea Index (AHI) > 30/h.

  • Contraindication to the use of Terazosin

    • Recent myocardial infarction (< 48 h)
    • Ongoing angina pectoris
    • Cardiogenic shock or prolonged
    • Breast feeding
    • Current use of Phosphodiesterase type 5 inhibitors: sildenafil (Viagra TM), tadalafil (Cialis TM), or vardenafil (Levitra TM)
    • History of Priapism
    • Neurogenic orthostatic hypotensiondefiened as symptomatic decrease in BP> 20 mmHg systolic or > 10mmHg diastolic and HR increase < 20bpm on supine to sitting or standing
    • Blood pressure less than 110 mmHG systolic at screening or baseline visit
    • Use of investigational drugs whitin 30 days before screening
    • For female participant, Pregnacy, or plans for child-bearing during study period
  • Allergy/hypersenstivity to iodine or study medication
Contacts and Locations
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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): NCT04386317


Contacts
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Contact: Michele L Gregorio, PhD 4243150016 michele.gregorio@cshs.org
Contact: Gloria Obialisi, MS 3104231704 gloria.obialisi@cshs.org

Locations
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United States, California
Cedars Sinai Medical Center Recruiting
Los Angeles, California, United States, 90048
Contact: Gloria Obialisi         
Sponsors and Collaborators
Cedars-Sinai Medical Center
More Information
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Responsible Party: Michele Tagliati, MD, Professor and Vice Chairman, Director of Movement Disorders, Cedars-Sinai Medical Center
ClinicalTrials.gov Identifier: NCT04386317    
Other Study ID Numbers: Study#000540
First Posted: May 13, 2020    Key Record Dates
Last Update Posted: August 26, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Parkinson Disease
REM Sleep Behavior Disorder
Parkinson Disease, Secondary
Mental Disorders
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Synucleinopathies
Neurodegenerative Diseases
 REM Sleep Parasomnias
Parasomnias
Sleep Wake Disorders
Terazosin
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Urological Agents