NCT02066571

Brief Summary

Since droxidopa has been approved in Japan for treating freezing of gait in Parkinson's disease patients, this is to confirm and further investigate the safety and efficacy using a similar dose. The possible beneficial effects on cognition in mildly cognitively impaired Parkinson's disease patients will also be tested, since this problem in Parkinson's disease may be associated with decreased brain synthesis of norepinephrine (a neurotransmitter associated with multiple brain functions). During this 11 week study, droxidopa will be slowly titrated up to 600 mg daily. Walking and freezing of gait will be evaluated and rated. Cognitive functions will be evaluated by a computer-based program.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
20

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Mar 2015

Typical duration for phase_2

Geographic Reach
1 country

2 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 18, 2014

Completed
1 day until next milestone

First Posted

Study publicly available on registry

February 19, 2014

Completed
1 year until next milestone

Study Start

First participant enrolled

March 1, 2015

Completed
2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2017

Completed
8 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2017

Completed
Last Updated

November 3, 2016

Status Verified

November 1, 2016

Enrollment Period

2.1 years

First QC Date

February 18, 2014

Last Update Submit

November 2, 2016

Conditions

Keywords

Parkinson's diseaseFreezing of gaitGait

Outcome Measures

Primary Outcomes (2)

  • Change from baseline in freezing of gait symptoms using Freezing of Gait Questionnaire

    Evaluate the effect of droxidopa on freezing of gait symptoms using the Freezing of Gait Questionnaire completed by patients. All measures will be performed at baseline and after two and four weeks of study medication.

    4 weeks

  • Change from baseline in cognitive testing

    Battery of cognitive testing is performed. All measures will be performed at baseline and after two and four weeks of study medication.

    4 weeks

Secondary Outcomes (4)

  • Change in measurement of freezing of gait

    4 weeks

  • Change in the incidence of falls

    4 weeks

  • Change in signs and symptoms of Parkinson's disease

    4 weeks

  • Number of participants with serious and non-serious adverse events

    up to 11 weeks

Study Arms (2)

droxidopa, then sugar pill

OTHER

Droxidopa will be titrated over a 2-week period up to 300 mg twice daily (600 mg total daily dose). Subjects will be titrated to highest tolerated dose and will continue on that dose for two weeks. Then, the subject will start sugar pills.

Drug: DroxidopaDrug: sugar pill

sugar pill, then droxidopa

OTHER

Subject will be be on sugar pill for 5 weeks (4 weeks of placebo treatment and one week of wash-out or sugar pills). Then, droxidopa will be titrated over 2 week period up to 300 mg twice daily (600 mg total daily dose). Subjects will be titrated to highest tolerated dose and will continue on that dose for two weeks.

Drug: DroxidopaDrug: sugar pill

Interventions

Droxidopa will be supplied in 100 and 200 mg pill sizes. The proposed dosing is 100mg twice daily at baseline, then titrate to 200 mg twice daily at day 7 and then titrate to 300mg twice daily at day 14. Subjects will stay on the 600mg daily for 2 weeks. Total exposure 28 days of study drug.

droxidopa, then sugar pillsugar pill, then droxidopa

Sugar pill or placebo will be supplied in pill sizes matched to droxidopa formulation. The study titration will be the same. Sugar pills will be used for 5 weeks during the study.

Also known as: placebo
droxidopa, then sugar pillsugar pill, then droxidopa

Eligibility Criteria

Age30 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Provide written informed consent to participate in the study
  • Diagnosed with probable levodopa-responsive idiopathic PD (meeting United Kingdom PD Brain Bank diagnostic criteria), and receiving levodopa therapy for this disorder. Other PD medications can also be used.
  • Must have AT LEAST ONE of below two criteria:
  • At least 3 months incidence of typical freezing of gait symptoms, occurring while levodopa is otherwise providing an "on" mobility state (including at least one of the following Freezing of Gait patterns: start hesitancy, freezing at making turns or when passing through a doorway, spontaneous freezing during continued walking, or Freezing of Gait related to a simultaneous mental or physical activity) OR
  • Have a screening score between 22 and 26 (inclusive) on the Montreal Cognitive Assessment

You may not qualify if:

  • Taking direct acting vasoconstriction agent (i.e. ephedrine or midodrine). Subjects taking vasoconstrictor agents such as ephedrine or midodrine must stop taking these drugs at least 2 days or 5 half-lives (whichever is longer) prior to their baseline visit
  • Taking anti-hypertensive medication for the treatment of hypertension. Anti-hypertensive medication taken at night to prevent supine hypertension will be allowed
  • Changing dose or frequency of PD medication within 2 weeks of baseline
  • Use of cognitive-enhancing medications (donepezil, galantamine, rivastigmine, tacrine, or memantine), catechol-O-methyltransferase inhibitors (tolcapone or entacapone), anticholinergic drugs, or antipsychotic drugs (including quetiapine or clozapine).
  • Known or suspected alcohol or substance abuse within 1 year (e.g. DSM-IV definition of alcoholism)
  • Past or current history of chronic severe hypertension (with repeated findings of BP 150/90 mmHg in the supine or standing position)
  • Symptomatic coronary artery disease, severe congestive heart failure (NYHA Class 3 or 4)
  • Unable to remain off any effective Freezing of Gait medications for 12 hrs prior to Evaluation visits)
  • Women who are pregnant, lactating, or plan to become pregnant during the course of this study
  • Women of child bearing potential who are not using two methods of contraception (at least one barrier, i.e. condom) with their partner.
  • Male subjects who are sexually active with a woman of child bearing potential and not using two methods of contraception (at least one barrier, for example, condom)
  • A history of closed angle glaucoma;
  • Active (in the last 6 months) atrial fibrillation or, in the investigator's opinion, any other significant cardiac arrhythmia that should preclude the subject from this trial
  • History of myocardial infarction or unstable angina
  • Congestive heart failure (NYHA Class 3 or 4)
  • +8 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Henry Ford Hospital, West Bloomfield

West Bloomfield, Michigan, 48322, United States

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

DroxidopaSugars

Condition Hierarchy (Ancestors)

Parkinsonian DisordersBasal Ganglia DiseasesBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesMovement DisordersSynucleinopathiesNeurodegenerative Diseases

Intervention Hierarchy (Ancestors)

NorepinephrineCatecholaminesAminesOrganic ChemicalsCatecholsPhenolsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsSerineAmino Acids, NeutralAmino AcidsAmino Acids, Peptides, and ProteinsCarbohydrates

Study Officials

  • Peter LeWitt, M.D.

    Henry Ford Health System

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
M.D.

Study Record Dates

First Submitted

February 18, 2014

First Posted

February 19, 2014

Study Start

March 1, 2015

Primary Completion

April 1, 2017

Study Completion

December 1, 2017

Last Updated

November 3, 2016

Record last verified: 2016-11

Locations