Safety and Efficacy of Droxidopa for Fatigue in Patients With Parkinsonism

Brief Title

Safety and Efficacy of Droxidopa for Fatigue in Patients With Parkinsonism

Official Title

Safety and Efficacy of Droxidopa for Fatigue in Patients With Parkinsonism

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.
    

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.
    

Study Phase

Phase 2

Study Type

Interventional

Primary Outcome

Efficacy of Droxidopa on fatigue in subjects with Parkinsonism as determined by completion of Visual Analogue Fatigue Scale (VAFS)

Secondary Outcome

 Efficacy of Droxidopa on motor and non-motor symptoms of Parkinsonism as determined by the Unified Parkinson's Disease Rating Scale (UPDRS)

Condition

Parkinson Disease

Intervention

Droxidopa

Study Arms / Comparison Groups

 Droxidopa

Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

0

Start Date

December 2021

Completion Date

July 1, 2023

Primary Completion Date

July 1, 2023

Eligibility 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)
      

Gender

All

Ages

50 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Khashayar Dashtipour, M.D. Ph.D., , 

Location Countries

United States

Location Countries

United States

NCT ID

NCT03446807

Organization ID

5170406

Responsible Party

Sponsor

Study Sponsor

Loma Linda University

Collaborators

 H. Lundbeck A/S

Study Sponsor

Khashayar Dashtipour, M.D. Ph.D., Principal Investigator, Loma Linda University Health

Verification Date

February 2022