- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02071459
Efficacy of L-threo DOPS on Orthostatic Hypotension Symptoms and Other Non-motor Symptoms in Patients With MSA (DOPS-AMS)
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
Study Overview
Status
Conditions
Intervention / Treatment
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
Enrollment (Actual)
Phase
- Phase 2
- Phase 3
Contacts and Locations
Study Locations
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-
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Angers, France, 49933
- Centre Hospitalier D'Angers
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Bordeaux, France
- CHU Bordeaux
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Clermont-Ferrand, France, 63000
- CHU de Clermont-Ferrand
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Dijon, France, 21000
- CHU de Dijon
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Lille, France, 59037
- CHRU de Lille
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Limoges, France, 87042
- CHU de Limoges
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Marseille, France, 13000
- Hôpital La Timone
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Nantes, France, 44093
- Hôpital G. & R. Laennec
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Paris, France, 75013
- Hôpital Pitié-Salpétrière
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Poitiers, France, 86021
- CHU de Poitiers
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Rennes, France, 35033
- CHU Pontchaillou
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Rouen, France, 76031
- CHU de Rouen
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Strasbourg, France, 67091
- CHU de Strasbourg
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: L-Threo DOPS
patients with Multiple System Atrophy (MSA) after 12 weeks to continued therapy with L-Threo DOPS
|
initial dose titration period (4 weeks) followed by 8 weeks at the max tolerated dose
Other Names:
|
Placebo Comparator: placebo
patients with Multiple System Atrophy (MSA) after 12 weeks to continued therapy with placebo
|
initial period (4 weeks) followed by 8 weeks
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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).
|
12 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
12 weeks
|
effects of L-Threo DOPS on motor symptoms
Time Frame: 12 weeks
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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
|
12 weeks
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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
|
12 weeks
|
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
|
12 Weeks
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Anne PAVY-LE-TRAON, PHD, CHU Toulouse
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Basal Ganglia Diseases
- Movement Disorders
- Synucleinopathies
- Neurodegenerative Diseases
- Pathological Conditions, Anatomical
- Autonomic Nervous System Diseases
- Primary Dysautonomias
- Orthostatic Intolerance
- Hypotension
- Atrophy
- Multiple System Atrophy
- Shy-Drager Syndrome
- Hypotension, Orthostatic
- Antiparkinson Agents
- Anti-Dyskinesia Agents
- Droxidopa
Other Study ID Numbers
- 12 554 01
- 12-018-0200 (Other Grant/Funding Number: French Ministry of Health, PHRC 2012)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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Clinical Trials on L-Threo DOPS
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Chelsea TherapeuticsCompletedFibromyalgiaUnited Kingdom
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Chelsea TherapeuticsTerminatedParkinson's Disease | Pure Autonomic Failure | Dopamine Beta Hydroxylase Deficiency | Symptomatic Neurogenic Orthostatic Hypotension | Multiple Systems AtrophyUnited States
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Chelsea TherapeuticsCompletedNeurogenic Orthostatic Hypotension | Primary Autonomic Failure | Dopamine Beta Hydroxylase Deficiency | Non-Diabetic Neuropathy
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Chelsea TherapeuticsChiltern International Inc.CompletedPrimary Autonomic Failure | Dopamine Beta Hydroxylase Deficiency | Symptomatic Neurogenic Orthostatic Hypotension (NOH) | Non-diabetic NeuropathyUnited States, Australia, Canada, New Zealand
-
Chelsea TherapeuticsWithdrawnGait Disorders, NeurologicUnited States, Canada
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Chelsea TherapeuticsCompletedParkinson's Disease | Orthostatic HypotensionUnited States
-
Vanderbilt UniversityApproved for marketing
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Chelsea TherapeuticsCompletedAttention Deficit Hyperactivity DisorderUnited States
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Bronx VA Medical CenterChelsea TherapeuticsCompletedHypotension | Spinal Cord InjuryUnited States