Clinical trial NCT02071459: Efficacy of L-threo DOPS on Orthostatic Hypotension Symptoms and Other Non-motor Symptoms in Patients With MSA
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Multiple System Atrophy
Keywords: L-threo DOPS (DroxiDopa)
Orthostatic Hypotension
Multiple system atrophy
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
First posted: 2014-02-25
Enrollment: 107
Sex: ALL
Minimum age (years): 30
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Evaluate the efficacy of long term efficacy of L-threo DOPS
timeFrame: 12 weeks
Secondary outcomes:
measure: efficacy of L-ThreoDOPS on symptomatic OH
timeFrame: 12 weeks
measure: effects of L-Threo DOPS on motor symptoms
timeFrame: 12 weeks
measure: effect of L-Threo DOPS on dysautonomic symptoms
timeFrame: 12 weeks
measure: safety of high doses of L-ThreoDOPS
timeFrame: 12 Weeks
Other outcomes:
Locations:
city: Angers
country: France
facility: Centre hospitalier d'Angers
city: Bordeaux
country: France
facility: CHU bordeaux
city: Clermont-Ferrand
country: France
facility: CHU de Clermont-Ferrand
city: Dijon
country: France
facility: CHU de Dijon
city: Lille
country: France
facility: CHRU de lille
city: Limoges
country: France
facility: CHU de limoges
city: Marseille
country: France
facility: Hôpital La Timone
city: Nantes
country: France
facility: Hôpital G. & R. Laennec
city: Paris
country: France
facility: Hôpital Pitié-Salpétrière
city: Poitiers
country: France
facility: CHU de Poitiers
city: Rennes
country: France
facility: CHU Pontchaillou
city: Rouen
country: France
facility: CHU de Rouen
city: Strasbourg
country: France
facility: chu de Strasbourg
Study officials:
affiliation: CHU Toulouse
name: Anne PAVY-LE-TRAON, PHD
role: PRINCIPAL_INVESTIGATOR
References: