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