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

Last updated: August 24, 2020
Sponsor: University Hospital, Toulouse
Overall Status: Completed

Phase

2/3

Condition

Multiple System Atrophy

Dizzy/fainting Spells

Vascular Diseases

Treatment

N/A

Clinical Study ID

NCT02071459
12 554 01
12-018-0200
  • Ages 30-80
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • MSA patients (possible or probable, MSA-P or C (according to revised criteria, Gilmanet 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 diastolicblood 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 weeksbefore the study and during the entire study

  • Signed written informed consent for the present study.

Exclusion

Exclusion Criteria:

  • Dementia (DSM-IV, Mini-Mental State Examination (MMSE) < 24/30)

  • Concomitant use of vaso-constrictive drugs, other than midodrine. Patients takingvasoconstrictor agents such as ephedrine, dihydroergotamine, must stop taking thesedrugs at least 2 days or 7 half-lives prior to their baseline visit (Visit 1); theassociation with midodrine may be kept at a stable dose not exceeding 3 tablets (7.5mg) / day if the patient has no CV history. This will be discussed case by case withthe coordinating center and the safety committee of this study.

  • Taking anti-hypertensive medication

Study Design

Total Participants: 107
Study Start date:
January 21, 2014
Estimated Completion Date:
October 28, 2019

Study 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.

Connect with a study center

  • Centre hospitalier d'Angers

    Angers, 49933
    France

    Site Not Available

  • CHU bordeaux

    Bordeaux,
    France

    Site Not Available

  • CHU de Clermont-Ferrand

    Clermont-Ferrand, 63000
    France

    Site Not Available

  • CHU de Dijon

    Dijon, 21000
    France

    Site Not Available

  • CHRU de lille

    Lille, 59037
    France

    Site Not Available

  • CHU de limoges

    Limoges, 87042
    France

    Site Not Available

  • Hôpital La Timone

    Marseille, 13000
    France

    Site Not Available

  • Hôpital G. & R. Laennec

    Nantes, 44093
    France

    Site Not Available

  • Hôpital Pitié-Salpétrière

    Paris, 75013
    France

    Site Not Available

  • CHU de Poitiers

    Poitiers, 86021
    France

    Site Not Available

  • CHU Pontchaillou

    Rennes, 35033
    France

    Site Not Available

  • CHU de Rouen

    Rouen, 76031
    France

    Site Not Available

  • chu de Strasbourg

    Strasbourg, 67091
    France

    Site Not Available

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