Polyamine-free Diet to Prevent Post Surgery Hyperalgesia (PoLyDOL)

December 24, 2009 updated by: University Hospital, Bordeaux

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

160

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 71 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Morphine requirement
Time Frame: for the 24 postoperative hours
for the 24 postoperative hours

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Bordeaux

Collaborators

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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2006

Primary Completion (Actual)

April 1, 2009

Study Completion (Actual)

May 1, 2009

Study Registration Dates

First Submitted

March 17, 2006

First Submitted That Met QC Criteria

March 17, 2006

First Posted (Estimate)

March 20, 2006

Study Record Updates

Last Update Posted (Estimate)

December 29, 2009

Last Update Submitted That Met QC Criteria

December 24, 2009

Last Verified

December 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 9258-03
  • 2002-004

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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