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

Toulouse University Hospital

Status and phase

Completed

Phase 3

Phase 2

Conditions

Multiple System Atrophy

Treatments

Drug: L-Threo DOPS

Drug: placebo

Study type

Interventional

Funder types

Other

Identifiers

NCT02071459

12-018-0200 (Other Grant/Funding Number)

12 554 01

Details and patient eligibility

About

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.

Full 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.

Enrollment

107 patients

Sex

All

Ages

30 to 80 years old

Volunteers

No Healthy Volunteers

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