Multiple symmetric lipomatosis

1
Il ruolo del blocco vagale nel trattamento
dellobesità e delle sue comorbidità.
Luca Busetto Dipartimento di Medicina -
Università di Padova Clinica Medica 1 Unità
Bariatrica
2
Nervo Vago Un elemento del sistema di
regolazione del bilancio energetico.
Ghrelin GLP-1/PYY
3
Nervo Vago Un potenziale target per il
trattamento dellobesità.
4

• Kral JG. Vagotomy for treatment of severe
  obesity. Lancet 197830307.
• Kral JG, Görtz L, Hermasson G, et al.
  Gastroplasty for obesity long-term
• weight loss improved by vagotomy. World J
  Surg 19931775.
• - Boss TJ, Trus T, Peters JH, et al.
  Laparoscopic truncal vagotomy for weight-loss
• a prospective, dual center safety and
  efficacy study. Surg Endosc 200822S146.
• Angrisani L, Cutolo PP, Ciciriello MB, et al.
  Laparoscopic adjustable gastric
• banding with truncal vagotomy versus
  laparoscopic adjustable gastric banding
• alone interim results of a prospective
  randomized trial. SOARD 20095435.
• Martin MB, Erle KR. Laparoscopic adjustable
  gastric banding with truncal
• vagotomy any increased weight loss? Surg
  Endosc 2011252522.

Kral JG et al. World J Surg 2009331995
5
VBLOC TherapyDelivered via the Maestro System

• VBLOC Therapy Blocco vagale intermittente
  durante le ore di veglia
• erogato da un pacemaker impiantato sottocute
  tramite due elettrodi
• fissati alla branca anteriore e posteriore
  del nervo vago a livello della
• giunzione gastro-esofagea.

6
VBLOC TherapyDelivered via the Maestro System
7
VBLOC Therapy procedura
8
Earlier Fullness and Less Hunger
Reduced Portion Size
Reduced Calories
30
Change from Baseline ()
40
Camilleri M et al. Surgery 2008143723
9
Sarr MG et al. Obes Surg 2012221771
10
EWL 172 vs 162
Sarr MG et al. Obes Surg 2012221771
11
Sarr MG et al. Obes Surg 2012221771
12
Sarr MG et al. Obes Surg 2012221771
13
Intermittent neural transmission block of the
intra-abdominal vagus induces sustained blood
pressure reduction in obese subcjets.
Tweden KS et al. AHA 2012 Abstr 13195
14
VBLOC Therapy2 generation device

• EMPOWER Trial
• (2008-2013)
• Randomized controlled trial in 294 obese patients
• 1st Generation RF device
• Endpoints
• Greater EWL for Treated v. Control
• Responder Analysis
• Safety
• Results
• Safety results were excellent
• An unanticipated therapeutic effect appeared to
  have been delivered to patients in the control
  arm thus comparative efficacy endpoint not met
• Dose effect -Clinically significant weight loss
  in patients who used the device 9 hours per day
  in treated and control groups

• ReCharge Study
• (2011-2016)
• Randomized controlled trial in 233 obese patients
• Builds on previous trial learning Similar design
  to EMPOWER trial and uses ENABLE device learning
• 2nd Generation device which averages 12 hours
  use
• No charge will be delivered to vagus nerve in the
  control group
• Endpoints
• Greater EWL for Treated v. Control
• Responder Analysis
• Safety
• Unblinding expected EOY 2012 announce results
  Q1 2013

15
RECHARGE Study Safety Results

• No deaths, no unanticipated adverse device
  effects.
• Implant/revision procedure, device,
  therapy-related SAEs in treated subjects (primary
  safety endpoint) 3.1 vs. 15 pre-specified
  limit, CI (1.0 - 7.1) plt0.0001.
• 93 of subjects were active in the blinded trial
  at 12 months.

16
RECHARGE Study Efficacy ResultsMean EWL in ITT
population.

Excess Weight Loss ()at 12 months (BMI) Treated Control Difference
N 162 77  
Mean SD 24.4 23.6 15.9 17.7 8.5 21.9
95 CI 20.8 - 28.1 11.9 - 19.9 3.1 - 13.9
gt10 Superiority P-value     0.705
Superiority P-value 0.002
17
RECHARGE Study
18
RECHARGE Study Efficacy ResultsResponders
Analysis in ITT Population.
Percent EWL achieved(BMI) TreatedN162 ControlN77 Odds Ratio p-Value
20 52.5 (85) 32.5 (25) 2.3 (1.3, 4.1) .004
25 38.3 (62) 23.4 (18) 2.1 (1.1, 3.8) .02
30 30.2 (49) 18.2 (14) 2.0 (1.0, 3.9) .047
35 25.9 (42) 9.1 (7) 3.5 (1.5, 8.3) .004
40 21.6 (35) 5.2 (4) 5.1 (1.7, 14.9) .003
45 18.5 (30) 3.9 (3) 5.7 (1.7, 19.2) .005
50 14.8 (24) 1.3 (1) 13.3 (1.8, 100.5) .01
19

RECHARGE StudyEfficacy results in Per Protocol
Population.
Excess Weight Loss ()at 12 months(BMI ) Treated Control Difference
N 146 65
Mean SD 26.3 23.8 17.3 18.1 8.9 22.2
95 CI 22.4 - 30.2 12.9 - 21.8 3.0 - 14.8
P-value (Delta 10) 0.640
P-value (Delta 0) 0.003
Percent EWL achieved (BMI) TreatedN146 ControlN65
20 56.8 (83) 35.4 (23)
25 41.8 (61) 26.2 (17)
20
VBLOC Therapy Conclusioni

• Il blocco intermittente della trasmissione
  nervosa a livello del vago intra-addominale è
  associato ad un significativo calo ponderale.
• Il calo ponderale con questa metodica è risultato
  significativamente superiore al placebo in uno
  studio randomizzato controllato.
• La tecnica appare sostanzialmente sicura e gli
  effetti collaterali molto ridotti.
• Possono esservi effetti sulla pressione
  indipendenti dal calo ponderale.