Polyamine-free Diet to Prevent Post Surgery Hyperalgesia

Phase 2

Completed

• Conditions: Breast Cancer; Surgery
• Interventions: Drug: Ketamine or placebo; Behavioral: polyamine-free diet

• Registration Number: NCT00304850
• Lead Sponsor: University Hospital, Bordeaux

Brief Summary

After surgery, sensitization and hyperexcitability of central nervous system result in acute and long lasting postoperative pain. It has been shown that N-methyl-D-aspartate (NMDA) receptors antagonist (such as ketamine) prevent this adverse neuroplasticity and potentiate analgesic drugs efficacy. Polyamines (putrescine, spermidine, spermine) are essential components of cells functioning and are also known as allosteric modulators of NMDA receptors. In animal studies, polyamine-free diet has confirmed these antinociceptive properties. This research aims at evaluating anti hyperalgesic properties of polyamine-free diet in women operated on breast cancer versus kétamine

Detailed Description

This multicentric, single blind study will enrol 160 women (18-75 years old) operated on tumorectomy and adenectomy (T1, T2, T3, N0, N1, M0) for breast cancer. Patients will be randomly assigned in a 2x2 factorial plan : Group 1 = control (n = 40) ; group 2 = ketamine group administered during and 48 hours after a standardized anesthesia (n = 40) ; group 3 = polyamine-free diet, 1 week and 72 hours after surgery (n = 40) ; group 4 : ketamine + polyamine-free diet (n = 40).

The amount of morphine for the 24 first postoperative hours will be compared between each group as well as pain score, allodynia (Von Frey filaments) and hyperalgesia (algometer). Chronic pain occurrence (post-mastectomy pain syndrome) will be evaluated at 3 and 6 months using adequate questionnaire ( analgesic scale). Diet observance will be controlled preoperatively by a dosage of polyamines in circulating red cells blood.

Polyamines deprivation and ketamine ability to reduce postoperative pain will be compared (isobolographic method). Anti-hyperalgesic properties of ketamine have already been demonstrated in urologic, orthopaedic and abdominal surgery. In case of additive or synergistic effect of a polyamine deprivation such a strategic could be helpful to achieve better postoperative rehabilitation in reducing chronic pain after surgery.

Study Timeline

• Study Start: 2006-03
• Study First Submitted: 2006-03-17
• Study First Submitted QC: 2006-03-17
• Study First Posted: 2006-03-20
• Primary Completion: 2009-04
• Study Completion: 2009-05
• Status Verified: 2009-12
• Last Update Submitted: 2009-12-24
• Last Update Posted: 2009-12-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 160

Inclusion Criteria

• Breast cancer (T1, T2, T3, N0, N1, M0)
• Age : 18 - 75
• Asa 1-3
• left or right tumorectomy with complete lymphadenectomy
• left or right complete mastectomy with complete lymphadenectomy
• complete lymphadenectomy within one week following simple tumorectomy
• informed consent signed

Exclusion Criteria

• inflammatory tumor requiring pre-operative radiotherapy
• previous history of total mastectomy or partial contralateral mastectomy
• chronic inflammatory disease treated by corticoids or NSAI
• chronic analgesic treatment
• anti-arrhythmic or anti-epileptic treatments
• morphinic treatment during the 7 days before surgery
• excessive alcohol consumption or addiction
• ketamine or neomycin contra-indication
• severe cardiovascular disease

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
R- / K+	Ketamine or placebo	-
R- /K-	Ketamine or placebo	-
R+ / K+	polyamine-free diet	-
R+ / K+	Ketamine or placebo	-
R+ / K-	polyamine-free diet	-
R+ / K-	Ketamine or placebo	-

Primary Outcome Measures

Name	Time	Method
Morphine requirement	for the 24 postoperative hours

Secondary Outcome Measures

Name	Time	Method
Pain intensity for the 4 days (and possibly at 7th day if the patient is still hospitalized) after surgery	4 days
Allodynia measurements	inclusion, 1, 2, 4 and 7 ddays after surgery
Hyperesthesia measurements	inclusion, 1, 2, 4 and 7 ddays after surgery
Chronic pain incidence	3 and 6 months
Late allodynia and/or hyperesthesia	6 months
safety of treatment	Along each patient folow-up

Trial Locations

Locations (5)

CLCC Alexis Vautrin; 🇫🇷 Nancy, France

CLCC-Institut Bergonie, service d'anesthésie réanimation, 229 cours de l'Argonne; 🇫🇷 Bordeaux, France

département d'anesthésie-réanimation 3, hôpital Pellegrin; 🇫🇷 Bordeaux, France

APHParis Hôpital Pitié Salpétrière - Dépt. d'anesthésie réanimation; 🇫🇷 Paris, France

CLCC Réné Huguenin de Saint Cloud; 🇫🇷 Saint Cloud, France