Polyamine-free Diet to Prevent Post Surgery Hyperalgesia

Breast Cancer Clinical Trial

— PoLyDOL  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00304850
• Other study ID #: 9258-03
• Secondary ID: 2002-004
• Status: Completed
• Phase: Phase 2
• First received: March 17, 2006
• Last updated: December 24, 2009
• Start date: March 2006
• Est. completion date: May 2009

Study information

• Verified date: December 2009
• Source: University Hospital, Bordeaux
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 160
• Est. completion date: May 2009
• Est. primary completion date: April 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 75 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Hyperalgesia
• Surgery

Intervention

Behavioral:
• polyamine-free diet
Polyamine-free diet in the 7 days befor surgery

Drug:
• Ketamine or placebo
Peroperative and post operative (48h) ketamine injection

Locations

Country	Name	City	State
France	CLCC-Institut Bergonie, service d'anesthésie réanimation, 229 cours de l'Argonne	Bordeaux
France	département d'anesthésie-réanimation 3, hôpital Pellegrin	Bordeaux
France	CLCC Alexis Vautrin	Nancy
France	APHParis Hôpital Pitié Salpétrière - Dépt. d'anesthésie réanimation	Paris
France	CLCC Réné Huguenin de Saint Cloud	Saint Cloud

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital, Bordeaux	Insurance CNP foundation, Ministry of Health, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Morphine requirement		for the 24 postoperative hours	No
Secondary	Pain intensity for the 4 days (and possibly at 7th day if the patient is still hospitalized) after surgery		4 days	No
Secondary	Allodynia measurements		inclusion, 1, 2, 4 and 7 ddays after surgery	No
Secondary	Hyperesthesia measurements		inclusion, 1, 2, 4 and 7 ddays after surgery	No
Secondary	Chronic pain incidence		3 and 6 months	No
Secondary	Late allodynia and/or hyperesthesia		6 months	No
Secondary	safety of treatment		Along each patient folow-up	Yes