Effect of Anti TNFa Upon Deep Endometriosis Associated Pain

NCT00604864 | Completed Phase 2 DMC

• 1 other identifier: trial_EU-0053/endometriosis
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Deep endometriosis associated pain is believed to be caused by inflammation. Anti TNFa has been proved to be an effective treatment for other inflammation related conditions as Crohn's disease Endometriosis is associated with an inflammatory response in the pelvis, which is mediated by a number of cytokines including TNF-α. It has therefore been suggested that infliximab, an anti-TNF-α monoclonal antibody, might relieve pain in affected women.

Conditions

Endometriosis

Keywords

deep endometriosis; pelvic pain; infliximab; anti TNFa

Outcome Measures

Primary Outcomes (1)

• Endometriosis associated pain

  By the clinician after 1, 2 and 3 months ; by the patient daily for 3 months

Secondary Outcomes (1)

• decrease in volume of deep endometriosis nodule

  after 1, 2 and 3 months of treatment

Study Arms (2)

1

EXPERIMENTAL

women with a deep endometriosis nodule of at least 1 cm in diameter; and severe pain (at least one severe pain score on Biberoglu Behrman scale)

Drug: anti TNFa monoclonal antibody - Infliximab

2

PLACEBO COMPARATOR

women with a deep endometriosis nodule of at least 1 cm in diameter; and severe pain (at least one severe pain score on Biberoglu Behrman scale)

Drug: placebo

Interventions

anti TNFa monoclonal antibody - Infliximab DRUG

Chimeric A2 (infliximab, RemicadeTM) IgG ; 100 mg infliximab IgG, Infliximab was freshly prepared immediately before each administration. Infliximab or placebo was administered as a slow infusion of 250mL on weeks 0, 2 and 6. Women were closely observed during, and for 1 hour after, the infusion in the event of any serious adverse reactions.

1

placebo DRUG

Placebo

2

Eligibility Criteria

• Age: 20 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• The patients (aged 18-50 years) were all recruited from a single, tertiary referral hospital at Leuven University, Belgium, specialising in the surgical treatment of severe endometriosis.
• All the women were symptomatic and scheduled for surgical excision of a rectovaginal nodule, at least 1 cm in diameter, diagnosed on the basis of clinical examination at the time of menstruation.
• All the women had a menstrual cycle occurring every 25 to 40 days.
• If previously treated with hormonal medication for endometriosis, at least 3 months must have elapsed and they must have had at least two menstrual cycles since stopping treatment.
• Unless the women had previously been sterilised, they had to agree to use a double-barrier method of contraception for the duration of the study and for up to 6 months after receiving the last infusion.
• The study was approved by the Institutional Review Board of Leuven University.
• Written, informed consent was obtained before any study related procedures were performed.

You may not qualify if:

• Evidence on chest x-ray in the previous 3 months of old or currently active TB, or other history/evidence of active TB, even if adequately treated
• Evidence of serious infections (such as pneumonia or pyelonephritis) in the previous 3 months
• Evidence of a documented HIV infection, active hepatitis-B or C, or an opportunistic infection (e.g. herpes zoster, cytomegalovirus, pneumocystis carinii, aspergillosis, histoplasmosis, or mycobacteria other than TB) in the previous 6 months
• Previous transplant surgery, a lymphoproliferative disorder or other malignancy
• Positive cervical cytology in the previous 6 months
• Previous treatment with infliximab, any drug known to affect TNF-α levels, e.g. pentoxifylline, thalidomide and etanercept, or any human/murine recombinant products
• Known allergy to murine products
• Use of other investigational drugs within 1 month of recruitment or within 5 half-lives of the investigational agent, whichever was longer
• Any haematological or biochemical abnormalities on routine screening.
• Subjects were also excluded if there was any pelvic pathology on transvaginal ultrasound scan (TVS) other than small uterine fibroids (\< 4 cm in diameter) and an ovarian endometrioma or endometriotic nodule.

Sponsors & Collaborators

• KU Leuven: lead

Study Sites (1)

University Hospital Gasthuisberg

Leuven, 3000, Belgium

Location

Related Publications (4)

• Anaf V, Simon P, El Nakadi I, Fayt I, Buxant F, Simonart T, Peny MO, Noel JC. Relationship between endometriotic foci and nerves in rectovaginal endometriotic nodules. Hum Reprod. 2000 Aug;15(8):1744-50. doi: 10.1093/humrep/15.8.1744.

  PMID: 10920097 BACKGROUND

• Colombel JF, Loftus EV Jr, Tremaine WJ, Pemberton JH, Wolff BG, Young-Fadok T, Harmsen WS, Schleck CD, Sandborn WJ. Early postoperative complications are not increased in patients with Crohn's disease treated perioperatively with infliximab or immunosuppressive therapy. Am J Gastroenterol. 2004 May;99(5):878-83. doi: 10.1111/j.1572-0241.2004.04148.x.

  PMID: 15128354 BACKGROUND

• D'Antonio M, Martelli F, Peano S, Papoian R, Borrelli F. Ability of recombinant human TNF binding protein-1 (r-hTBP-1) to inhibit the development of experimentally-induced endometriosis in rats. J Reprod Immunol. 2000 Oct-Nov;48(2):81-98. doi: 10.1016/s0165-0378(00)00073-5.

  PMID: 11011074 BACKGROUND

• Koninckx PR, Craessaerts M, Timmerman D, Cornillie F, Kennedy S. Anti-TNF-alpha treatment for deep endometriosis-associated pain: a randomized placebo-controlled trial. Hum Reprod. 2008 Sep;23(9):2017-23. doi: 10.1093/humrep/den177. Epub 2008 Jun 12.

  PMID: 18556683 DERIVED

MeSH Terms

Conditions

Endometriosis; Pelvic Pain

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Philippe R Koninckx, MD, PhD

  Catholic University Leuven

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: January 17, 2008
• First Posted: January 30, 2008
• Study Start: February 1, 2004
• Primary Completion: February 1, 2005
• Study Completion: November 1, 2005
• Last Updated: January 30, 2008

Record last verified: 2008-01

Locations

BE (1)