REM Sleep Behavior Disorder Clinical Trial
Official title:
The Effect of a1- Adrenergic Receptor Antagonist Therapy on Cardiac and Striatal Transporter Uptake in Pre-Motor and Symptomatic Parkinson's Disease
Parkinson's disease (PD) is characterized by many non-motor symptoms that occur several years before the diagnosis, in particular idiopathic REM behavior disorder (iRBD), which is associated with autonomic impairment. The purpose of this study is to investigate the effect of treatment with the selective post-synaptic a1-adrenergic blocker terazosin on 123I-MIBG myocardial uptake in a population of subjects with defined pre-motor PD risks (i.e. hyposmia and RBD) and abnormal baseline 123I-MIBG uptake, with or without 123I-Ioflupane uptake abnormality or PD motor symptoms. Scintigraphic changes will be correlated to motor and non-motor severity of PD, measured by validated clinical scales and cardiac autonomic function tests.
Status | Recruiting |
Enrollment | 15 |
Est. completion date | December 30, 2025 |
Est. primary completion date | December 30, 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 50 Years to 85 Years |
Eligibility | Inclusion Criteria: - Male or female of age between 50 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 |
Country | Name | City | State |
---|---|---|---|
United States | Michele L Lima Gregorio | Los Angeles | California |
Lead Sponsor | Collaborator |
---|---|
Cedars-Sinai Medical Center |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | 1) Differences in 123I-MIBG reuptake, as measured by early and late H/M ratio, and WR, at 26 weeks of treatment with the adrenergic blocker Terazosin. | At baseline and at 26 weeks after medication titration | |
Secondary | Incidence of adverse events | Safety will be monitored collecting the type and frequency of adverse events, including clinical symptoms | At baseline and at 26 weeks after medication titration | |
Secondary | Heart Rate variability changes from baseline at 26 weeks after study medication titration | Beat-to-beat intervals will be registered to assess sympatho-vagal balance. | At baseline and at 26 weeks after medication titration | |
Secondary | Incidence of abnormal vital signs | Changes in vital signs (Blood pressure and Heart rate) | At baseline and at 26 weeks after medication titration |
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