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

This study has been completed.
Sponsor:
Collaborators:
Ministry of Health, France
Insurance CNP foundation
Information provided by:
University Hospital, Bordeaux
ClinicalTrials.gov Identifier:
NCT00304850
First received: March 17, 2006
Last updated: December 24, 2009
Last verified: December 2009
  Purpose

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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University Hospital, Bordeaux:

Primary Outcome Measures:
  • Morphine requirement [ Time Frame: for the 24 postoperative hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pain intensity for the 4 days (and possibly at 7th day if the patient is still hospitalized) after surgery [ Time Frame: 4 days ] [ Designated as safety issue: No ]
  • Allodynia measurements [ Time Frame: inclusion, 1, 2, 4 and 7 ddays after surgery ] [ Designated as safety issue: No ]
  • Hyperesthesia measurements [ Time Frame: inclusion, 1, 2, 4 and 7 ddays after surgery ] [ Designated as safety issue: No ]
  • Chronic pain incidence [ Time Frame: 3 and 6 months ] [ Designated as safety issue: No ]
  • Late allodynia and/or hyperesthesia [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • safety of treatment [ Time Frame: Along each patient folow-up ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 160
Study Start Date: March 2006
Study Completion Date: May 2009
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00304850

Locations
France
département d'anesthésie-réanimation 3, hôpital Pellegrin
Bordeaux, France, 33076
CLCC-Institut Bergonie, service d'anesthésie réanimation, 229 cours de l'Argonne
Bordeaux, France, 33000
CLCC Alexis Vautrin
Nancy, France, 54511
APHParis Hôpital Pitié Salpétrière - Dépt. d'anesthésie réanimation
Paris, France, 75013
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
  More Information

No publications provided

Responsible Party: Jean-Pierre LEROY / Clinical Research and Innovation Director, University Hospital, Bordeaux
ClinicalTrials.gov Identifier: NCT00304850     History of Changes
Other Study ID Numbers: 9258-03, 2002-004
Study First Received: March 17, 2006
Last Updated: December 24, 2009
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Bordeaux:
polyamines
pain
breast cancer
mastectomy
post operative pain

Additional relevant MeSH terms:
Breast Neoplasms
Hyperalgesia
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Somatosensory Disorders
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Ketamine
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Analgesics
Sensory System Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on July 24, 2014