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

NCT ID: NCT02071459

Last Updated: 2020-08-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 107 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-21
• Study Completion Date: 2019-10-28

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.

Conditions

Multiple System Atrophy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

L-Threo DOPS

patients with Multiple System Atrophy (MSA) after 12 weeks to continued therapy with L-Threo DOPS

Group Type: EXPERIMENTAL

L-Threo DOPS

Intervention Type: DRUG

initial dose titration period (4 weeks) followed by 8 weeks at the max tolerated dose

placebo

patients with Multiple System Atrophy (MSA) after 12 weeks to continued therapy with placebo

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

initial period (4 weeks) followed by 8 weeks

Interventions

L-Threo DOPS

initial dose titration period (4 weeks) followed by 8 weeks at the max tolerated dose

Intervention Type: DRUG

placebo

initial period (4 weeks) followed by 8 weeks

Intervention Type: DRUG

Other Intervention Names

L DOPS or DroxiDopa

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

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Toulouse

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anne PAVY-LE-TRAON, PHD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Toulouse

Locations

Centre hospitalier d'Angers

Angers, , France

CHU bordeaux

Bordeaux, , France

CHU de Clermont-Ferrand

Clermont-Ferrand, , France

CHU de Dijon

Dijon, , France

CHRU de lille

Lille, , France

CHU de limoges

Limoges, , France

Hôpital La Timone

Marseille, , France

Hôpital G. & R. Laennec

Nantes, , France

Hôpital Pitié-Salpétrière

Paris, , France

CHU de Poitiers

Poitiers, , France

CHU Pontchaillou

Rennes, , France

CHU de Rouen

Rouen, , France

chu de Strasbourg

Strasbourg, , France

Countries

France

Other Identifiers

12-018-0200

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

12 554 01

Identifier Type: -

Identifier Source: org_study_id