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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by University Hospital, Toulouse
Sponsor:
Information provided by (Responsible Party):
University Hospital, Toulouse
ClinicalTrials.gov Identifier:
NCT02071459
First received: February 21, 2014
Last updated: August 28, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Multiple System Atrophy
Drug: L-Threo DOPS
Drug: placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by University Hospital, Toulouse:

Primary Outcome Measures:
  • Evaluate the efficacy of long term efficacy of L-threo DOPS [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • efficacy of L-ThreoDOPS on symptomatic OH [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    Determine the safety of high doses of L-ThreoDOPS in MSA patients based on the occurrence of treatment-emergent adverse events


Estimated Enrollment: 108
Study Start Date: February 2014
Estimated Study Completion Date: February 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: L-Threo DOPS
patients with Multiple System Atrophy (MSA) after 12 weeks to continued therapy with L-Threo DOPS
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
Placebo Comparator: placebo
patients with Multiple System Atrophy (MSA) after 12 weeks to continued therapy with placebo
Drug: placebo
initial period (4 weeks) followed by 8 weeks

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.

  Eligibility

Ages Eligible for Study:   30 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • MSA patients (possible or probable , MSA-P or C (according to revised criteria , Gilman et al 2008)).
  • Men and women 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))
  • And 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, MMSE < 24/30)
  • Concomitant use of vaso-constricitve 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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02071459

Contacts
Contact: ANNE PAVY-LE-TRAON, PHD 33(0)561772271 pavy-letraon.a@chu-toulouse.fr

Locations
France
Centre hospitalier d'Angers Recruiting
Angers, France, 49933
Contact: Valérie Chauviré, PHD       vachauvire@chu-angers.fr   
Principal Investigator: valerie chauvire, PHD         
CHU bordeaux Recruiting
Bordeaux, France
Contact: françois Tison, PHD    05 57 65 64 20    francois.tison@chu-bordeaux.fr   
Principal Investigator: François Tison, PHD         
CHU de Clermont-Ferrand Recruiting
Clermont-Ferrand, France, 63000
Contact: Miguel Ulla, PHD    04 73 75 15 94    mulla@chu-clermontferrand.fr   
CHU de Dijon Recruiting
Dijon, France, 21000
Contact: thibault Moreau, PHD    03 80 29 37 53    thibault.moreau@chu-dijon.fr   
Principal Investigator: Thibault moreau, PHD         
CHRU de lille Recruiting
Lille, France, 59037
Contact: Luc Defebvre, PHD    03.20.44.67.52    luc.defebvre@chru-lille.fr   
Principal Investigator: Luc Defebvre, PHD         
CHU de limoges Recruiting
Limoges, France, 87042
Contact: Frédéric Torny, PHD    05 55 05 65 61    frederic.torny@chu-limoges.fr   
Principal Investigator: Frédéric Torny, PHD         
Hôpital La Timone Recruiting
Marseille, France, 13000
Contact: Alexandre Eusebio, PHD    04 91 38 43 33    Alexandre.Eusebio@ap-hm.fr   
Principal Investigator: Alexandre Eusebio, PHD         
Hôpital G. & R. Laennec Not yet recruiting
Nantes, France, 44093
Contact: pascal. derkinderen, PHD       pascal.derkinderen@chu-nantes.fr   
Principal Investigator: pascal. derkinderen, PHD         
Hôpital Pitié-Salpétrière Recruiting
Paris, France, 75013
Contact: Jean-Christophe Corvol, PHD    01 42 16 19 50    jean-christophe.corvol@psl.aphp.fr   
Principal Investigator: jean-christophe. corvol, PHD         
CHU de Poitiers Not yet recruiting
Poitiers, France, 86021
Contact: Jean-Luc Houeto, PHD    05 49 44 44 46    j.l.houeto@chu-poitiers.fr   
Principal Investigator: Jean-Luc Houeto, PHD         
CHU Pontchaillou Not yet recruiting
Rennes, France, 35033
Contact: Dr Sophie Drapier, PHD    02 99 28 98 42    sophie.drapier@chu-rennes.fr   
Principal Investigator: sophie. drapier, PHD         
CHU de Rouen Recruiting
Rouen, France, 76031
Contact: David Maltête, PHD       david.maltete@chu-rouen.fr   
Principal Investigator: david. maltete, PHD         
chu de Strasbourg Not yet recruiting
Strasbourg, France, 67091
Contact: Christine Tranchant, PHD    03 88 11 53 66    christine.tranchant@chru-strasbourg.fr   
Principal Investigator: : christine. tranchant, PHD         
Sponsors and Collaborators
University Hospital, Toulouse
Investigators
Principal Investigator: Anne PAVY-LE-TRAON, PHD CHU Toulouse
  More Information

No publications provided

Responsible Party: University Hospital, Toulouse
ClinicalTrials.gov Identifier: NCT02071459     History of Changes
Other Study ID Numbers: 1255401, 12-018-0200
Study First Received: February 21, 2014
Last Updated: August 28, 2014
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by University Hospital, Toulouse:
L-threo DOPS (DroxiDopa)
Orthostatic Hypotension
Multiple system atrophy

Additional relevant MeSH terms:
Atrophy
Multiple System Atrophy
Shy-Drager Syndrome
Autonomic Nervous System Diseases
Central Nervous System Diseases
Nervous System Diseases
Central Nervous System Agents
Hypotension
Hypotension, Orthostatic
Basal Ganglia Diseases
Brain Diseases
Cardiovascular Diseases
Movement Disorders
Neurodegenerative Diseases
Orthostatic Intolerance
Pathological Conditions, Anatomical
Primary Dysautonomias
Vascular Diseases
Droxidopa
Anti-Dyskinesia Agents
Antiparkinson Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014