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Efficacy of L-threo DOPS on Orthostatic Hypotension Symptoms and Other Non-motor Symptoms in Patients With MSA (DOPS-AMS)

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ClinicalTrials.gov Identifier: NCT02071459
Recruitment Status : Unknown
Verified March 2017 by University Hospital, Toulouse.
Recruitment status was:  Recruiting
First Posted : February 25, 2014
Last Update Posted : March 7, 2017
Sponsor:
Information provided by (Responsible Party):
University Hospital, Toulouse

Tracking Information
First Submitted Date  ICMJE February 21, 2014
First Posted Date  ICMJE February 25, 2014
Last Update Posted Date March 7, 2017
Study Start Date  ICMJE February 2014
Estimated Primary Completion Date December 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 21, 2014)
Evaluate the efficacy of long term efficacy of L-threo DOPS [ Time Frame: 12 weeks ]
Evaluate the efficacy of long term efficacy of L-threo DOPS (droxidopa) in MSA patients (probable or possible - cerebellar (C) or parkinsonian (P) type) with symptomatic NOH as measured by the relative change in mean score of Orthostatic Hypotension Symptom Assessment (OHSA) (Part I of the questionnaire on the symptoms OH (OHQ) (Kaufmann et al., 2011)) 12 weeks following randomization to therapy with droxidopa or placebo (including 8 weeks to maximum tolerated dose).
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02071459 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 21, 2014)
  • efficacy of L-ThreoDOPS on symptomatic OH [ Time Frame: 12 weeks ]
    Evaluate and compare the efficacy of L-ThreoDOPS on symptomatic OH (measured by the relative change in mean score of Item 1 of the Orthostatic Hypotension Symptom Assessment (OHSA)) in MSA patients 4, 8 and 12 weeks following randomization to continued therapy with droxidopa or placebo
  • effects of L-Threo DOPS on motor symptoms [ Time Frame: 12 weeks ]
    Evaluate the effects of L-Threo DOPS on motor symptoms (UMSARS I and II) in MSA patients after 12 weeks following randomization to continued therapy with droxidopa or placebo
  • effect of L-Threo DOPS on dysautonomic symptoms [ Time Frame: 12 weeks ]
    Evaluate the effect of L-Threo DOPS on dysautonomic symptoms (COMPASS) in MSA patients after 4, 8 and 12 weeks following randomization to continued therapy with droxidopa or placebo
  • safety of high doses of L-ThreoDOPS [ Time Frame: 12 Weeks ]
    Determine the safety of high doses of L-ThreoDOPS in MSA patients based on the occurrence of treatment-emergent adverse events
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy of L-threo DOPS on Orthostatic Hypotension Symptoms and Other Non-motor Symptoms in Patients With MSA
Official Title  ICMJE Evaluate the Long-term (3 Months) Efficacy of L-threo DOPS (DroxiDopa) on Orthostatic Hypotension Symptoms and Other Non-motor Symptoms in Patients With Multiple System Atrophy (MSA). Comparative Study Versus Placebo
Brief Summary Evaluate the effects of L-Threo DOPS on orthostatic hypotension symptoms and other non-motor symptoms in patients with Multiple System Atrophy (MSA) after 12 weeks following randomization to continued therapy with droxidopa or placebo.
Detailed Description

Background :

Multiple system atrophy (MSA) is a rare, sporadic progressive neurodegenerative disorder, rapidly leading to severe disability and impairment of quality of life. MSA is characterized by a variable combination of a poor levodopa parkinsonism and /or cerebellar ataxia and autonomic failure (cardiovascular and / or bladder and sexual dysfunction) (Gilman et al, 2008). The prevalence is approximately 4-5 cases per 100 000 inhabitants.

Orthostatic hypotension (OH) is one of the major symptoms of MSA, present in a large majority of patients, leading to significant disability because of impaired balance, falls and possibly syncope. Drugs available to treat OH in this disease are very limited.

L-ThreoDOPS (L DOPS or DroxiDopa) is an orally administered synthetic catecholamine acid that is converted to the sympathetic neurotransmitter norepinephrine (NE) through a single step of decarboxylation by the endogenous enzyme 3,4-dihydroxyphenylalanine (DOPA) decarboxylase. It prevents symptoms related to OH by central and/peripheral mechanisms. This drug is currently developed for "neurogenic OH" by Chelsea Therapeutics on the basis of short duration placebo-controlled randomized trials. Besides an expected effect on OH, L-DOPS may also, by noradrenergic stimulation, improve some motor and non-motor symptoms common and disabling in MSA patients such as akinesia and fatigue.

In this context, the French reference center for MSA and the 12 national centers with identified skills to manage this disease, propose to conduct a national multicenter randomized clinical trial versus placebo to evaluate the long term efficacy (3 months) of L-threo DOPS on the OH and other non-motor symptoms in MSA patients.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Multiple System Atrophy
Intervention  ICMJE
  • Drug: L-Threo DOPS
    initial dose titration period (4 weeks) followed by 8 weeks at the max tolerated dose
    Other Name: L DOPS or DroxiDopa
  • Drug: placebo
    initial period (4 weeks) followed by 8 weeks
Study Arms  ICMJE
  • Experimental: L-Threo DOPS
    patients with Multiple System Atrophy (MSA) after 12 weeks to continued therapy with L-Threo DOPS
    Intervention: Drug: L-Threo DOPS
  • Placebo Comparator: placebo
    patients with Multiple System Atrophy (MSA) after 12 weeks to continued therapy with placebo
    Intervention: Drug: placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: February 21, 2014)
108
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2018
Estimated Primary Completion Date December 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • MSA patients (possible or probable, MSA-P or C (according to revised criteria, Gilman et al 2008)).
  • Aged 30 to 80 years,
  • Able to walk at least 10 meters
  • With symptomatic OH (score of at least 3 at one of the items of Part I of the OH scale (OHQ))
  • Documented fall in systolic blood pressure of at least 20 mmHg, and/or in diastolic blood pressure of at least 10 mmHg, within 3 minutes after standing.
  • Able to fill in the evaluation questionnaires with or without help
  • With no significant problems with swallowing.
  • Stable anti-parkinsonian, dysautonomia and depression treatments for the 4 weeks before the study and during the entire study
  • Signed written informed consent for the present study.

Exclusion Criteria:

  • Dementia (DSM-IV, Mini-Mental State Examination (MMSE) < 24/30)
  • Concomitant use of vaso-constrictive drugs, other than midodrine. Patients taking vasoconstrictor agents such as ephedrine, dihydroergotamine, must stop taking these drugs at least 2 days or 7 half-lives prior to their baseline visit (Visit 1); the association with midodrine may be kept at a stable dose not exceeding 3 tablets (7.5 mg) / day if the patient has no CV history. This will be discussed case by case with the coordinating center and the safety committee of this study.
  • Taking anti-hypertensive medication
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 30 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02071459
Other Study ID Numbers  ICMJE 12 554 01
12-018-0200 ( Other Grant/Funding Number: French Ministry of Health, PHRC 2012 )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University Hospital, Toulouse
Study Sponsor  ICMJE University Hospital, Toulouse
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Anne PAVY-LE-TRAON, PHD CHU Toulouse
PRS Account University Hospital, Toulouse
Verification Date March 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP