Study of the Effects on Motor Recovery of Early Post-stroke Spasticity Treatment

NCT02462317 | Completed Phase 4

• 2 other identifiers: 10 140 012010-022881-28
• Study Type: interventional
• Target: 184
• Locations: 1 country
• Sites: 19

Brief Summary

Stroke is the first cause of motor impairment and disability in adults. Then the main objective of rehabilitation during the first six months following stroke is to facilitate motor recovery. Many post-stroke hemiplegics develop spasticity which is responsible for an increase of disability. Then antispastic drugs are frequently prescribed to the patients even during the post-stroke recovery phase. Until recently most of french patients were treated by oral tablets of baclofen. Now the number of patients receiving intramuscular injections of botulinum A toxin is increasing. However in the literature, these drugs have been tested in post-stroke spasticity during the chronicle phase, after the sixth month and their action on motor recovery remain largely unknown. Then it is necessary to evaluate more accurately the effects of its drugs on motor recovery. The main criterion of its study is the time course of Fugl-Meyer Motor Assessment (FMA). Spastic patients with a single stroke, since less than two months, will be included in the try. They receive at the same time oral tablets for five months and intramuscular injections. Patients are randomized in three arms planned with a distribution balanced by group of 5 patients with a 2 -2- 1 model: botulinum toxin and placebo baclofen (120 patients), oral baclofen and placebo botulinum toxin (120 patients), placebo baclofen and placebo botulinum toxin (60 patients). The FMA score will be assessed before treatment start, one month and three months later. Spasticity, functional abilities, capacity in the activities of daily life, pain and quality of life will be also assessed during the study with Tardieu score, Rivermead Motor Assessment scale, Barthel index, Rankin score, Visual Analogic Scale and Reintegration to Normal Life Index respectively. A positive difference of 12 points in the time course of FMA in the botulinum toxin group in comparison with the baclofen group will be considered as the minimum relevant effect. 300 patients have been planned to be included in 20 centers during the 2 years of trial.

Conditions

Muscle Spasticity

Keywords

Spasticity; Post stroke motor recovery; Botulinum toxin; Baclofen; Pharmacological modulation

Outcome Measures

Primary Outcomes (1)

• Motor recovery with time course of Fugl-Meyer Assessment scale

  A positive difference of 12 points in the time of course of Fugl-Meyer motor Assessment scale (FMA) from inclusion to the third month, between the results obtained in the botulinum toxin group and those of the baclofen group will be considered as the minimum relevant effect.

  month 3

Secondary Outcomes (5)

• none inferiority of motor recovery with time course of Fugl-Meyer Assessment scale

  month 3

• Spasticity with Tardieu scale

  Month 1 and 3

• Function with Rivermead Motor Assessment score,

  month 3

• Quality of life : Reintegration to Normal Life Index

  month 3

• Pain : Visual Analogic Scale

  Month 1 and 3

Study Arms (3)

botulinum A toxin

ACTIVE COMPARATOR

Patients are injected with botulinum toxin in a standardized protocol and received placebo baclofen tablets (120 patients)

Drug: botulinum A toxin; Drug: placebo baclofen

Baclofen

ACTIVE COMPARATOR

Patients are injected with placebo in a standardized protocol and received baclofen tablets (120 patients)

Drug: Baclofen; Drug: Placebo toxin

double Placebo

PLACEBO COMPARATOR

Patients are injected with placebo in a standardized protocol and received placebo baclofen tablets (60 patients)

Drug: Placebo toxin; Drug: placebo baclofen

Interventions

botulinum A toxin DRUG

botulinum toxin injection

Also known as: Drug injection

botulinum A toxin

Baclofen DRUG

baclofen oral tablet

Also known as: Drug

Baclofen

Placebo toxin DRUG

placebo injection

Also known as: placebo injection

Baclofen; double Placebo

placebo baclofen DRUG

placebo oral tablet

Also known as: placebo drug

botulinum A toxin; double Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• First single stroke ischaemic or haemorrhagic responsible of an hemiplegia
• Stoke since less than 2 month
• A sufficient understood
• A spasticity : a Tardieu score upper or equal to 2 on at least one of the following muscle-triceps surae, flexors of fingers, of wrist and of elbow
• A free consent

You may not qualify if:

• Previous antispastic drugs
• Contraindication for baclofen or toxin
• Antecedent of epileptic seizure
• Psychiatric antecedent

Sponsors & Collaborators

• University Hospital, Toulouse: lead
• Merz Pharmaceuticals GmbH: collaborator

Study Sites (19)

University Hospital, Toulouse

Toulouse, Haute-Garonne, 31059, France

Location

CHU Jean Minjoz

Besançon, 25030, France

Location

Groupe Pellegrin, University Hospital Bordeaux

Bordeaux, 33076, France

Location

CHRU de Brest

Brest, 29609, France

Location

Centre de rééducation MARIENIA

Cambo-les-Bains, 64250, France

Location

Centre Bouffard- Vercelli

Cervera de la Marenda, 66290, France

Location

University Hospital Dijon

Dijon, 21079, France

Location

University Hospital Grenoble

Échirolles, 38434, France

Location

Hôpital R. Poincarré

Garches, 92380, France

Location

l'Institut Hélio Marin de la côte d'azur

Hyères, 67082, France

Location

Hôpital Swynghedauw

Lille, 59000, France

Location

Hôpital J Rebeyrol

Limoges, 87042, France

Location

CHU Gui de Chauliac

Montpellier, 34295, France

Location

University Hospital Carémeau

Nîmes, 30029, France

Location

Hopital Rothschild

Paris, 75012, France

Location

GH Lariboisière F.Widal

Paris, 75013, France

Location

Groupe Hospitalier Pitié-Salpêtrière

Paris, 75013, France

Location

Université Reims Champagne Ardenne

Reims, 51092, France

Location

Pôle MPR St Hélier

Rennes, 35000, France

Location

Related Publications (15)

• Jorgensen HS, Nakayama H, Raaschou HO, Vive-Larsen J, Stoier M, Olsen TS. Outcome and time course of recovery in stroke. Part II: Time course of recovery. The Copenhagen Stroke Study. Arch Phys Med Rehabil. 1995 May;76(5):406-12. doi: 10.1016/s0003-9993(95)80568-0.

  PMID: 7741609 BACKGROUND

• Jorgensen HS, Nakayama H, Raaschou HO, Vive-Larsen J, Stoier M, Olsen TS. Outcome and time course of recovery in stroke. Part I: Outcome. The Copenhagen Stroke Study. Arch Phys Med Rehabil. 1995 May;76(5):399-405. doi: 10.1016/s0003-9993(95)80567-2.

  PMID: 7741608 BACKGROUND

• Kwakkel G, Kollen B, Twisk J. Impact of time on improvement of outcome after stroke. Stroke. 2006 Sep;37(9):2348-53. doi: 10.1161/01.STR.0000238594.91938.1e. Epub 2006 Aug 24.

  PMID: 16931787 BACKGROUND

• Kwakkel G, van Peppen R, Wagenaar RC, Wood Dauphinee S, Richards C, Ashburn A, Miller K, Lincoln N, Partridge C, Wellwood I, Langhorne P. Effects of augmented exercise therapy time after stroke: a meta-analysis. Stroke. 2004 Nov;35(11):2529-39. doi: 10.1161/01.STR.0000143153.76460.7d. Epub 2004 Oct 7.

  PMID: 15472114 BACKGROUND

• Feeney DM, Gonzalez A, Law WA. Amphetamine, haloperidol, and experience interact to affect rate of recovery after motor cortex injury. Science. 1982 Aug 27;217(4562):855-7. doi: 10.1126/science.7100929.

  PMID: 7100929 BACKGROUND

• Goldstein LB, Davis JN. Physician prescribing patterns following hospital admission for ischemic cerebrovascular disease. Neurology. 1988 Nov;38(11):1806-9. doi: 10.1212/wnl.38.11.1806.

  PMID: 3185921 BACKGROUND

• Goldstein LB, Davis JN. Clonidine impairs recovery of beam-walking after a sensorimotor cortex lesion in the rat. Brain Res. 1990 Feb 5;508(2):305-9. doi: 10.1016/0006-8993(90)90413-6.

  PMID: 2306622 BACKGROUND

• Goldstein LB. Influence of common drugs and related factors on stroke outcome. Curr Opin Neurol. 1997 Feb;10(1):52-7. doi: 10.1097/00019052-199702000-00011.

  PMID: 9099528 BACKGROUND

• Goldstein LB. Potential effects of common drugs on stroke recovery. Arch Neurol. 1998 Apr;55(4):454-6. doi: 10.1001/archneur.55.4.454.

  PMID: 9561971 BACKGROUND

• Goldstein LB. Effects of amphetamines and small related molecules on recovery after stroke in animals and man. Neuropharmacology. 2000 Mar 3;39(5):852-9. doi: 10.1016/s0028-3908(99)00249-x.

  PMID: 10699450 BACKGROUND

• Goldstein LB. Neurotransmitters and motor activity: effects on functional recovery after brain injury. NeuroRx. 2006 Oct;3(4):451-7. doi: 10.1016/j.nurx.2006.07.010.

  PMID: 17012058 BACKGROUND

• Tardy J, Pariente J, Leger A, Dechaumont-Palacin S, Gerdelat A, Guiraud V, Conchou F, Albucher JF, Marque P, Franceries X, Cognard C, Rascol O, Chollet F, Loubinoux I. Methylphenidate modulates cerebral post-stroke reorganization. Neuroimage. 2006 Nov 15;33(3):913-22. doi: 10.1016/j.neuroimage.2006.07.014. Epub 2006 Sep 14.

  PMID: 16978883 BACKGROUND

• Crisostomo EA, Duncan PW, Propst M, Dawson DV, Davis JN. Evidence that amphetamine with physical therapy promotes recovery of motor function in stroke patients. Ann Neurol. 1988 Jan;23(1):94-7. doi: 10.1002/ana.410230117.

  PMID: 3345072 BACKGROUND

• Walker-Batson D, Smith P, Curtis S, Unwin H, Greenlee R. Amphetamine paired with physical therapy accelerates motor recovery after stroke. Further evidence. Stroke. 1995 Dec;26(12):2254-9. doi: 10.1161/01.str.26.12.2254.

  PMID: 7491646 BACKGROUND

• Montane E, Brihmat N, Cormier C, Thalamas C, Rousseau V, Tap G, De Boissezon X, Castel-Lacanal E; Baclotox Group; Marque P. Effect of Early Treatment of Spasticity After Stroke on Motor Recovery: Protocol for the Baclotox Multicenter, Double-Blind, Double-Dummy Randomized Controlled Trial. JMIR Res Protoc. 2025 May 9;14:e62951. doi: 10.2196/62951.

  PMID: 40344664 DERIVED

MeSH Terms

Conditions

Muscle Spasticity

Interventions

Botulinum Toxins, Type A; Pharmaceutical Preparations; Baclofen

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors; gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Philippe MARQUE, MD, PhD

  University Hospital, Toulouse

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2015
• First Posted: June 4, 2015
• Study Start: April 1, 2015
• Primary Completion: December 9, 2019
• Study Completion: December 9, 2020
• Last Updated: February 1, 2021

Record last verified: 2021-01

Locations

FR (19)