il ruolo del blocco vagale nel trattamento dell’obesità e delle sue comorbidità. luca busetto...
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Il ruolo del blocco vagale nel trattamento dell’obesità e delle sue
comorbidità.Luca Busetto
Dipartimento di Medicina - Università di PadovaClinica Medica 1 – Unità Bariatrica
Ghrelin GLP-1/PYY
Nervo Vago: Un elemento del sistema di regolazione del bilancio energetico.
80% delle fibre vagali sono AFFERENTI
(dallo stomaco al SNC)
20% delle fibre vagali sono EFFERENTI
(dal SNC allo stomaco)
MOTORIE– Secrezione acida gastrica– Secrezione enzimi digestivi– Capacità gastrica– Svuotamento gastrico
SENSITIVE–Fame –Sazietà–Metabolismo energetico–Regolazione pressoria
Nervo Vago: Un potenziale target per il trattamento dell’obesità.
Kral JG et al. World J Surg 2009;33:1995
- Kral JG. Vagotomy for treatment of severe obesity. Lancet 1978;30:307.
- Kral JG, Görtz L, Hermasson G, et al. Gastroplasty for obesity: long-term weight loss improved by vagotomy. World J Surg 1993;17:75.
- Boss TJ, Trus T, Peters JH, et al. Laparoscopic truncal vagotomy for weight-loss a prospective, dual center safety and efficacy study. Surg Endosc 2008;22:S146.
- 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 2009;5:435.
- Martin MB, Erle KR. Laparoscopic adjustable gastric banding with truncal vagotomy: any increased weight loss? Surg Endosc 2011;25:2522.
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.
VBLOC TherapyDelivered via the Maestro System
VBLOC Therapy: procedura
(40%)
(35%)
(30%)
(25%)
(20%)
(15%)
(10%)
(5%)
0%
5%
10%
15%
20%
25%
30%
% EWL from Implant
Calories (kcal %)
Pre-implant 4 weeks 12 weeks 6 months
Protein Carbohydrates Fat
0
250
500
750
1000
1250
1500
1750
2000
2250
Pre-implant
(n=10)
4 weeks
(n=10)12 weeks
(n=8)6 months
(n=9)
20%
43%
37%
20%
44%
36%
23%
41%
22%
40%
38%36%
(90)%
(60)%
(30)%
0%
30%
60%
90%
Reduced hunger
Ch
ange
fro
m B
asel
ine
(%)
Therapy Initiation 4 weeks 12 weeks 6 months
Earlier fullness
Earlier Fullness and Less Hunger Reduced Portion Size Reduced Calories
Ch
ange
fro
m B
asel
ine
(%)
30
40
Camilleri M et al. Surgery 2008;143:723
Sarr MG et al. Obes Surg 2012;22:1771
Sarr MG et al. Obes Surg 2012;22:1771
%EWL 17±2 vs 16±2 %
Sarr MG et al. Obes Surg 2012;22:1771
Red
uct
ion
in B
lood
Pre
ssu
re (
mm
Hg)
Week 2 Week 4 12 MonthsBaseline BP 145/89 145/89 145/89
Ending BP 128/80 128/81 127/79
Systolic Blood Pressure Diastolic Blood Pressure
Sarr MG et al. Obes Surg 2012;22:1771
Intermittent neural transmission block of the intra-abdominal vagus induces sustained blood pressure reduction in obese subcjets.
-10
-9
-8
-7
-6
-5
-4
-3
-2
-1
0
-30
-25
-20
-15
-10
-5
0
0 1 2 3 4 5 6 7 8 9 10 11 12
Chan
ge in
DBP
(mm
Hg)
%EW
L
Months from Implant
%EWL and Change in DBP among Empower Subjects with >= 9 Hours Average Use through 12 Months and History of Hypertension at Baseline
(Note: Baseline is Screening for BP and Implant for EWL - BP measured in triplicate at BL, 6 and 12 months only)
%EWL Change in DBP
Tweden KS et al. AHA 2012 Abstr 13195
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
VBLOC Therapy2^ generation device
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%); p<0.0001.
93% of subjects were active in the blinded trial at 12 months.
RECHARGE Study: Safety Results
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]
>10% Superiority P-value 0.705
Superiority P-value 0.002
RECHARGE Study: Efficacy ResultsMean %EWL in ITT population.
RECHARGE Study
Percent EWL achieved
(BMI)TreatedN=162
ControlN=77 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
RECHARGE Study: Efficacy ResultsResponders Analysis in ITT Population.
Excess Weight Loss (%)at 12 months
(BMI ) Treated Control Difference
N 146 65Mean ± 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) TreatedN=146
ControlN=65
20% 56.8% (83) 35.4% (23)25% 41.8% (61) 26.2% (17)
RECHARGE Study:Efficacy results in Per Protocol Population.
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.
VBLOC Therapy: Conclusioni