Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety and Efficacy of Droxidopa for Fatigue in Patients With Parkinsonism

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03446807
Recruitment Status : Not yet recruiting
First Posted : February 27, 2018
Last Update Posted : March 12, 2018
Sponsor:
Collaborator:
H. Lundbeck A/S
Information provided by (Responsible Party):
Loma Linda University

Brief Summary:
The purpose of this study is to determine the efficacy of Droxidopa for the treatment of fatigue in patients with Parkinsonism by the Visual Analog Fatigue Scale (VAFS). This is a randomized, placebo-controlled, double-blind clinical trial for 3 months where half the subjects will receive placebo and the other half will receive Droxidopa. Following this will be a wash-out period of 7 days and then all subjects will receive Droxidopa for 3 months during the open-label phase.

Condition or disease Intervention/treatment Phase
Parkinson Disease Multiple System Atrophy Progressive Supranuclear Palsy Drug: Droxidopa Drug: Placebo Oral Tablet Phase 2

Detailed Description:

Parkinsonism, is a group of symptoms seen in several diseases, including Parkinson's Disease. In Parkinsonism, a patient may become stiff, have smaller and slower movements, develop a tremor (shaking of the arms or legs), have decreased facial expression, and a softer voice.

Fatigue is a common symptom that causes suffering and stress in diseases that affect the brain. Over 50% of patients with Parkinsonism report fatigue as one of their top three symptoms that make their life more difficult. Currently, there are no evidence-based guidelines for treating fatigue in Parkinson's Disease, and no effective medications or therapeutic modalities exist for fatigue symptoms in patients with Parkinson's Disease.

Droxidopa (also known by the trade name NORTHERA) is a safe and well tolerated medication which has been approved in USA for the treatment of orthostatic dizziness or light headedness in patients with a clinical diagnosis of symptomatic Neurogenic Orthostatic Hypotension associated with primary autonomic failure (Parkinson's Disease and Multiple System Atrophy), Dopamine Beta Hydroxylase Deficiency, or Non Diabetic Autonomic Neuropathy.

Fatigue may be due to diminished levels of norepinephrine in Parkinson's Disease. The locus coeruleus, one of the major sources of norepinephrine, is affected during the preclinical phase of Parkinson's Disease during stage 2 of Braak pathology staging. Norepinephrine is the final metabolite of dopamine, therefore by adding exogenous norepinephrine, it may be possible to control some of the motor and non-motor symptoms of Parkinsonism. Norepinephrine is the final metabolite of droxidopa, and it is still unclear if it passes the blood-brain barrier. This pilot study is to measure the efficacy and safety of droxidopa in Parkinsonism patients with fatigue.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description: The first phase is double-blind and the second phase is open label.
Primary Purpose: Treatment
Official Title: Safety and Efficacy of Droxidopa for Fatigue in Patients With Parkinsonism
Estimated Study Start Date : April 2018
Estimated Primary Completion Date : March 1, 2019
Estimated Study Completion Date : April 1, 2019


Arm Intervention/treatment
Experimental: Droxidopa
The Droxidopa starting dose for all eligible patients in the Titration Periods are 100mg three times daily (TID). Doses will be titrated by 100mg TID; increments will be made weekly until the optimal dose is achieved or the subject doesn't notice an improvement in their subjective fatigue on a higher dose compared to the most recent dose. Half of the subjects will be on Droxidopa for 3 months during the double-blind phase. All subjects will be on Droxidopa for 3 months during the open-label phase.
Drug: Droxidopa
Droxidopa in 100, 200, and 300mg capsules. Maximum dose to be used in this study is 600mg.
Other Name: Northera

Placebo Comparator: Placebo Oral Tablet
The placebo starting dose for all eligible patients in the Titration Period is 100mg TID. Doses will be titrated by 100mg TID; increments will be made weekly until the optimal dose is achieved. Half of the subjects will be on placebo for 3 months during the double-blind phase.
Drug: Placebo Oral Tablet
Placebo capsules to match Droxidopa 100, 200, and 300mg capsules.
Other Name: Placebo




Primary Outcome Measures :
  1. Efficacy of Droxidopa on fatigue in subjects with Parkinsonism as determined by completion of Visual Analogue Fatigue Scale (VAFS) [ Time Frame: Change between baseline and 12 weeks ]
    Subjects will complete the VAFS which measures level of fatigue with zero being equivalent to energetic with no fatigue to ten being worst possible fatigue

  2. Efficacy of Droxidopa on fatigue in subjects with Parkinsonism as determined by completion of Visual Analogue Fatigue Scale (VAFS) [ Time Frame: Change between 18 weeks and 28 weeks ]
    Subjects will complete the VAFS which measures level of fatigue with zero being equivalent to energetic with no fatigue to ten being worst possible fatigue

  3. Efficacy of Droxidopa on fatigue in subjects with Parkinsonism as determined by completion of Visual Analogue Fatigue Scale (VAFS) [ Time Frame: Week 29 ]
    Subjects will complete the VAFS which measures level of fatigue with zero being equivalent to energetic with no fatigue to ten being worst possible fatigue


Secondary Outcome Measures :
  1. Efficacy of Droxidopa on motor and non-motor symptoms of Parkinsonism as determined by the Unified Parkinson's Disease Rating Scale (UPDRS) [ Time Frame: Change between baseline and 12 weeks ]
    The UPDRS is a composite measurement of motor and non-motor symptoms divided into six domains. Domain I measures Mentation, Behavior and Mood. Domain II measures Activities of Daily Living. Domain III measures Motor Examination. Domain IV measures Complications of Therapy. Domain V is Modified Hoehn and Yahr Staging. Domain 6 is Schwab and England Activities of Daily Living Scale

  2. Efficacy of Droxidopa on motor and non-motor symptoms of Parkinsonism as determined by the Unified Parkinson's Disease Rating Scale (UPDRS) [ Time Frame: Change between 18 weeks and 28 weeks ]
    The UPDRS is a composite measurement of motor and non-motor symptoms divided into six domains. Domain I measures Mentation, Behavior and Mood. Domain II measures Activities of Daily Living. Domain III measures Motor Examination. Domain IV measures Complications of Therapy. Domain V is Modified Hoehn and Yahr Staging. Domain 6 is Schwab and England Activities of Daily Living Scale

  3. Efficacy of Droxidopa on motor and non-motor symptoms of Parkinsonism as determined by the Unified Parkinson's Disease Rating Scale (UPDRS) [ Time Frame: Week 29 ]
    The UPDRS is a composite measurement of motor and non-motor symptoms divided into six domains. Domain I measures Mentation, Behavior and Mood. Domain II measures Activities of Daily Living. Domain III measures Motor Examination. Domain IV measures Complications of Therapy. Domain V is Modified Hoehn and Yahr Staging. Domain 6 is Schwab and England Activities of Daily Living Scale



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age of 50 years or older.
  • Clinical diagnosis of Parkinsons Disease or Atypical Parkinsonism (including multiple system atrophy (MSA), PSP)
  • Fluent in English
  • Reported fatigue and must have a mean VAFS score of 4 or more at baseline
  • Written informed consent

Exclusion Criteria:

  • Inability to understand or cooperate with study procedures
  • Alcohol or substance use disorder within the past 12 months (as per Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria)
  • Women who are pregnant or breastfeeding
  • Women of childbearing potential (WOCP) as indicated by one of the following:
  • Sustained supine hypertension greater than or equal to 180 mmHg systolic or 110 mmHg diastolic. Sustained is defined as the average of 3 observations each at least 10 minutes apart with the patient having been supine and at rest for at least 5 minutes prior to each measurement
  • Untreated closed angle glaucoma
  • Diagnosis of hypertension that requires treatment with antihypertensive medications
  • 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)
  • Diabetic autonomic neuropathy
  • 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
  • Gastrointestinal condition that may affect the absorption of Investigational Medicinal Product (e.g. ulcerative colitis, gastric bypass)
  • Any major surgical procedure within 30 days prior to the first titration visit.
  • Currently receiving any investigational drug or have received an investigational drug within 28 days prior to the first titration visit
  • Any condition or laboratory test result, which in the Investigator's judgment, might result in an increased risk to the patient, or would affect their participation in the study
  • Dementia or non-treated depression
  • Subjects who have a mean VAFS score of less than 4 at baseline
  • Vulnerable populations
  • Uncontrolled intercurrent illnesses including, but not limited to severe lung disease, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic cardiac arrhythmia, and situations that would limit compliance with study requirements will be excluded
  • Orthostatic hypotension (OH)

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): NCT03446807


Contacts
Layout table for location contacts
Contact: Principal Investigator 909-558-2037 KDashtipour@llu.edu
Contact: Charles E Kamen, M.D. 909-558-2037 CKamen@llu.edu

Locations
Layout table for location information
United States, California
Loma Linda University Faculty Medical Offices - Neurology Clinic Not yet recruiting
Loma Linda, California, United States, 92354
Contact: Khashayar Dashtipour, MD, PhD    909-558-2037    KDashtipour@llu.edu   
Contact: Charles E Kamen, MD    909-558-2037    CKamen@llu.edu   
Sponsors and Collaborators
Loma Linda University
H. Lundbeck A/S
Investigators
Layout table for investigator information
Principal Investigator: Khashayar Dashtipour, M.D. Ph.D. Loma Linda University Health
  Study Documents (Full-Text)

Documents provided by Loma Linda University:
Study Protocol  [PDF] February 13, 2018


Publications:

Layout table for additonal information
Responsible Party: Loma Linda University
ClinicalTrials.gov Identifier: NCT03446807     History of Changes
Other Study ID Numbers: 5170406
First Posted: February 27, 2018    Key Record Dates
Last Update Posted: March 12, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Lundbeck is funding this study and will be providing the study drug. If Lundbeck requests, they will be provided with protocol, statistical analysis plan, clinical study report, and any other study data they request. All adverse events will be reported to Lundbeck.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: The data will be available to Lundbeck from the start of the study through it's completion.
Access Criteria: This material will be provided to Lundbeck in person, not electronically.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Loma Linda University:
fatigue
Droxidopa
Additional relevant MeSH terms:
Layout table for MeSH terms
Multiple System Atrophy
Shy-Drager Syndrome
Brain Diseases
Parkinson Disease
Supranuclear Palsy, Progressive
Parkinsonian Disorders
Fatigue
Atrophy
Basal Ganglia Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Signs and Symptoms
Pathological Conditions, Anatomical
Primary Dysautonomias
Autonomic Nervous System Diseases
Hypotension
Vascular Diseases
Cardiovascular Diseases
Ophthalmoplegia
Ocular Motility Disorders
Cranial Nerve Diseases
Tauopathies
Paralysis
Neurologic Manifestations
Eye Diseases
Droxidopa
Antiparkinson Agents
Anti-Dyskinesia Agents