Norepinephrine-targeted Therapy for Action Control in Parkinson Disease

NCT03115827 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: VUMC54580
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to find out whether droxidopa, a medication that increases norepinephrine levels, may be effective in improving some aspects of cognition and movement in Parkinson's disease (PD).

Conditions

Parkinson Disease

Outcome Measures

Primary Outcomes (2)

• Number of Subjects Who Develop an Adverse Event During the 7-week Treatment Period That is Determined to be Likely Related to the Study Medications.

  Safety will be defined by the percent of subjects who develop an adverse event during the 7-week treatment period that is determined to be likely related to the study medications.

  7 weeks

• Number of Participants Who Discontinue the Study Drug Due to Adverse Effects During the 7-week Treatment Period.

  Tolerability will be defined by the number of patients who discontinue the study drug due to adverse effects.

  7 weeks

Secondary Outcomes (3)

• Maximum Tolerated Dose

  Week 4 to Week 7

• Percent Compliance

  7 weeks

• Change in Stop-Signal Reaction Time From Baseline to Week 7

  baseline and week 7

Study Arms (1)

Arm 1

EXPERIMENTAL

Droxidopa 600mg by mouth twice a day and carbidopa 200mg by mouth twice a day for 4 weeks

Drug: Droxidopa; Drug: Carbidopa

Interventions

Droxidopa DRUG

Droxidopa will be started at 100mg twice a day and titrated up to a maximum of 600mg twice a day

Arm 1

Carbidopa DRUG

Carbidopa 200mg twice a day

Arm 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Nondemented man or woman 18 years of age or older with idiopathic PD based on the UK Parkinson Disease Society Brain Bank Clinical Diagnostic Criteria (refer to Appendix C for the criteria)
• Unified Parkinson Disease Rating Scale (UPDRS) motor scores OFF medication consistent with postural instability gait difficulty (PIGD) subtype
• Symptoms of freezing or falls
• Able to walk at least 10 meters
• Medically stable outpatient, based on the investigator's judgment
• The patient must be willing and able to give written informed consent prior to performing any study procedures.

You may not qualify if:

• Score of 21 or lower on Montreal Cognitive Assessment
• Sustained supine hypertension greater than or equal to 180 mmHg systolic or 110 mmHg diastolic, or have these measurements at their Baseline Visit (Visit 2). Sustained is defined as measurements persistently greater at 2 separate measurements at least 10 minutes apart with the subject supine and at rest for at least 5 minutes.
• Concomitant use of vasoconstricting agents such as ephedrine, dihydroergotamine, or midodrine. Concomitant use of other noradrenergic medications, such as serotonin-norepinephrine reuptake inhibitors (SNRI's) is also contraindicated. Patients must stop taking these drugs at least 2 days or 5 half-lives (whichever is longer) prior to their baseline visit and throughout the duration of the study.
• Diagnosis of hypertension that requires treatment with antihypertensive medications (short-acting antihypertensives to treat nocturnal supine hypertension are allowed in this study)
• Women of childbearing potential
• Any significant uncontrolled cardiac arrhythmia
• History of myocardial infarction, within the past 2 years
• Current unstable angina
• Congestive heart failure (NYHA Class 3 or 4)
• History of cancer within the past 2 years other than a successfully treated, non-metastatic cutaneous squamous cell or basal cell carcinoma or cervical cancer in situ
• History of stroke
• Gastrointestinal condition that may affect the absorption of study drug (e.g., ulcerative colitis, gastric bypass)
• Musculoskeletal disorders such as severe arthritis, post knee surgery, hip surgery, or any other condition that the investigators determine may impair assessment of gait
• History of myocardial infarction, uncontrolled cardiac arrhythmia, unstable angina, congestive heart failure, or stroke
• Untreated closed angle glaucoma

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• H. Lundbeck A/S: collaborator
• American Academy of Neurology: collaborator

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

Droxidopa; Carbidopa

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Norepinephrine; Catecholamines; Amines; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Serine; Amino Acids, Neutral; Amino Acids; Amino Acids, Peptides, and Proteins; Methyldopa; Dihydroxyphenylalanine; Hydrazines

Limitations and Caveats

This study was an open-label, dose-titration, safety and tolerability pilot study with a small sample size (n=15). Additionally, there was no placebo arm or comparison group.

Results Point of Contact

• Title: Dr. Katherine McDonell
• Organization: Vanderbilt University Medical Center

katherine.mcdonell@vumc.org

615-875-7987

Study Officials

• Katherine McDonell, MD

  Vanderbilt Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Masking Details: All patients will receive the same treatment.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Neurology

Model Details: This is a single-arm study enrolling 15 patients that will all receive the experimental treatment.

Study Record Dates

• First Submitted: March 9, 2017
• First Posted: April 14, 2017
• Study Start: April 18, 2017
• Primary Completion: December 21, 2018
• Study Completion: December 21, 2018
• Last Updated: January 27, 2020
• Results First Posted: January 27, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)