SPINAL MUSCULAR ATROPHY RANDOMISED TRIAL ItalianSMART Gabapentin

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SPINAL MUSCULAR ATROPHYRANDOMISED
TRIALItalian-SMART(Gabapentin)

• LUCIANO MERLINI, Istituto Ortopedico Rizzoli,
  Bologna
• ENRICO BERTINI, Ospedale Bambino Gesù, IRCCS,
  Roma
• CARLO MINETTI, Istituto G. Gaslini, Università di
  Genova
• TIZIANA MONGINI, Centro Malattie Neuromuscolari,
  Univ. di Torino
• LUCIA MORANDI, Istituto Neurologico C. Besta,
  Milano
• GIUSEPPE VITA, Clinica Neurologica, Policlinico
  Universitario di Messina
• CORRADO ANGELINI, Dipartimento di Neurologia,
  Università di Padova

AME, Barcelona 2005
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SMART story - 8

• 6 Months Trial Design
• 6 Months Funding
• 6 Months Drug and Ethical Committee approval
• 3 Months Patients recruitment
• 12 Months Treatment
• 3 Months Statistical analysis
• TOTAL TIME 3 YEARS
• December 1998 November 2001

AME, Barcelona 2005
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IOR
Elbow Flexion test
Subject supine, shoulder adducted, elbow 90
flexed, forearm pronated, with the dynamometer
just proximal to flexor wrist crease.
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IOR
Grip test

• The subject is seated, shoulder adducted, elbow
  90 flexed
• Tester holds the dynamometer upright

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SMART Trial - 1

• Patients, Centres, Treatment

• 120 patients, aged 5-60 yrs, with SMA and SMN
  gene mutation
• Stratification (5-12 yrs over 12 yrs), and
  randomization
• Gabapentin 50 mg/kg or up to 1800 mg in 6 weeks,
  b.i.d.
• Treatment period 12 months

AME, Barcelona 2005
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SMART Trial - 2

• Trial Design
• Multicenter, randomized, open, comparative,
  parallel-group (previously, double-blind and
  placebo controlled) trial of gabapentin in SMA 2
  and 3.
• Following the Good Clinical Practice guidelines
• Primary End-point 35 increment of Arm Megascore
• Secondary End-point 35 increment of Leg Megascore

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SMART results 1
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SMART results 2
ARM MEGASCORE, d
Study Group Control Group
Mean (95CI)
Mean (95CI) P value 6 mo.
14.8 ( 5.4 24.2) 4.8
(-2.1 - 11.8) 0.12 12 mo. 21.1
(11.5 30.6) 6.3 (-4.7 17.3)
0.04
ITT
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SMART results 3
LEG MEGASCORE, d
Study Group Control Group
Mean (95CI)
Mean (95CI) P value 6 mo.
29.9 (13.2 - 46.6) 4.8
(-2.1 - 11.8) 0.02 12 mo. 32.7
(16.6 - 48.9) 6.6 (-2.7 - 15.9)
0.01
ITT
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SMART results 4
ITALIAN SMART - Study flow chart          

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SMART results 5
ITALIAN SMART - Study flow chart          
Merlini L, Bertini E, Minetti C, Mongini T,
Morandi L, Angelini C, Vita G. Motor
function-muscle strength relationship in spinal
muscular atrophy. Muscle Nerve. 2004
Apr29(4)548-52.

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European SPINAL MUSCULAR ATROPHYRANDOMISED
TRIALEuroSMART(L-acetyl-carnitine vs. placebo)

• IRENA HAUSMANOWA-PETRUSEWICZ, Warsaw, Poland
• EDUARDO TIZZANO, Barcelona, Spain
• THOMAS VOIT, Essen, Germany
• HALUK TOPALOGLU, Ankara, Univ. Turkey
• YEHUDA SHAPIRA, Jerusalem, Israel
• LUCIANO MERLINI, Bologna, Italy

AME, Barcelona 2005