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| ID | Type | Description | Link |
|---|---|---|---|
| 12-018-0200 | Other Grant/Funding Number | French Ministry of Health, PHRC 2012 |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| L-Threo DOPS | Experimental | patients with Multiple System Atrophy (MSA) after 12 weeks to continued therapy with L-Threo DOPS |
|
| placebo | Placebo Comparator | patients with Multiple System Atrophy (MSA) after 12 weeks to continued therapy with placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| L-Threo DOPS | Drug | initial dose titration period (4 weeks) followed by 8 weeks at the max tolerated dose |
|
| Measure | Description | Time Frame |
|---|---|---|
| Evaluate the efficacy of long term efficacy of L-threo DOPS | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| efficacy of L-ThreoDOPS on symptomatic OH | 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Anne PAVY-LE-TRAON, PHD | University Hospital, Toulouse | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centre hospitalier d'Angers | Angers | 49933 | France | |||
| CHU bordeaux |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41269291 | Result | Dierickx LO, Bettiol C, Huglo D, Marcelli F, Sibert L, Gouel P, Ferretti L, Orlhac F, Huyghe E. Is 18F-fluorodexyglucose testicular uptake using positron emission tomography/computed tomography correlated with the results of a testicular sperm extraction procedure in the case of azoospermia (French prospective multicenter AZOPREDHISTOTEP study)? Eur J Nucl Med Mol Imaging. 2026 Apr;53(5):3283-3290. doi: 10.1007/s00259-025-07583-7. Epub 2025 Nov 21. |
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| placebo | Drug | initial period (4 weeks) followed by 8 weeks |
|
| effects of L-Threo DOPS on motor symptoms |
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 |
| effect of L-Threo DOPS on dysautonomic symptoms | 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 | Determine the safety of high doses of L-ThreoDOPS in MSA patients based on the occurrence of treatment-emergent adverse events | 12 Weeks |
| Bordeaux |
| France |
| CHU de Clermont-Ferrand | Clermont-Ferrand | 63000 | France |
| CHU de Dijon | Dijon | 21000 | France |
| CHRU de lille | Lille | 59037 | France |
| CHU de limoges | Limoges | 87042 | France |
| Hôpital La Timone | Marseille | 13000 | France |
| Hôpital G. & R. Laennec | Nantes | 44093 | France |
| Hôpital Pitié-Salpétrière | Paris | 75013 | France |
| CHU de Poitiers | Poitiers | 86021 | France |
| CHU Pontchaillou | Rennes | 35033 | France |
| CHU de Rouen | Rouen | 76031 | France |
| chu de Strasbourg | Strasbourg | 67091 | France |
| ID | Term |
|---|---|
| D019578 | Multiple System Atrophy |
| D007024 | Hypotension, Orthostatic |
| ID | Term |
|---|---|
| D054969 | Primary Dysautonomias |
| D001342 | Autonomic Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |
| D054971 | Orthostatic Intolerance |
| D007022 | Hypotension |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D015103 | Droxidopa |
| ID | Term |
|---|---|
| D009638 | Norepinephrine |
| D002395 | Catecholamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D002396 | Catechols |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D012694 | Serine |
| D021542 | Amino Acids, Neutral |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
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