PoLyDOL: Polyamine-free Diet to Prevent Post Surgery Hyperalgesia

Sponsor

University Hospital, Bordeaux (Other)

Overall Status

Completed

CT.gov ID

NCT00304850

Collaborator

Ministry of Health, France (Other), Insurance CNP foundation (Other)

160

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Surgery	Behavioral: polyamine-free diet Drug: Ketamine or placebo	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

160 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Efficacy of a Polyamine-free Diet Associated or Not With Ketamine on Early and Late Hyperalgesia After Breast Cancer Surgery

Study Start Date :

Mar 1, 2006

Actual Primary Completion Date :

Apr 1, 2009

Actual Study Completion Date :

May 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: R+ / K+	Behavioral: polyamine-free diet Polyamine-free diet in the 7 days befor surgery Drug: Ketamine or placebo Peroperative and post operative (48h) ketamine injection
Experimental: R+ / K-	Behavioral: polyamine-free diet Polyamine-free diet in the 7 days befor surgery Drug: Ketamine or placebo Peroperative and post operative (48h) ketamine injection
Experimental: R- / K+	Drug: Ketamine or placebo Peroperative and post operative (48h) ketamine injection
Placebo Comparator: R- /K-	Drug: Ketamine or placebo Peroperative and post operative (48h) ketamine injection

Outcome Measures

Primary Outcome Measures

Morphine requirement [for the 24 postoperative hours]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	CLCC-Institut Bergonie, service d'anesthésie réanimation, 229 cours de l'Argonne	Bordeaux	France	33000
2	département d'anesthésie-réanimation 3, hôpital Pellegrin	Bordeaux	France	33076
3	CLCC Alexis Vautrin	Nancy	France	54511
4	APHParis Hôpital Pitié Salpétrière - Dépt. d'anesthésie réanimation	Paris	France	75013
5	CLCC Réné Huguenin de Saint Cloud	Saint Cloud	France	92210

Sponsors and Collaborators

University Hospital, Bordeaux
Ministry of Health, France
Insurance CNP foundation

Investigators

Principal Investigator: Pierre MAURETTE, Pr, DAR 3 -Pellegrin hospital-33076 Bordeaux - France
Study Chair: Genevieve CHENE, Pr, University hospital - 33076 Bordeaux - France