Clinical trial NCT00237523: Study for Treatment of Moderate or Severe, Periodic, "Cyclic", Breast Pain
Official title: A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of IoGen™ for the Treatment of Moderate or Severe, Periodic Breast Pain Associated With Symptomatic Fibrocystic Breast Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Fibrocystic Disease of Breast
Fibrocystic Changes of Breast
Fibrocystic Mastopathy
Pain
Keywords: Breast pain
Mastalgia
Cyclic mastalgia
Periodic mastalgia
Non-cyclic mastalgia
Fibrosis
Nodularity
Cysts
Fibrocystic breast disease
Fibrocystic breast condition
Fibocystic breast syndrome
Lead sponsor: Symbollon Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2005-10-12
Enrollment: 175
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: * History of clinical breast pain for at least the last six months.
* At least six days of moderate or severe breast pain per cycle.
* Fibrosis, cysts, nodules involving at least 25% of the surface of one breast.
* Euthyroid with no prior history of thyroid disease.
* Six months of daily therapy with molecular iodine.
* Placebo controlled vs active (1:1).

Detailed description: Primary efficacy parameters will be measured by patient self-assessment of pain/tenderness using a categorical daily pain diary. Clinical pain is defined as a patient assessment of moderate or severe pain for any given day. Total clinical pain per menstrual cycle is calculated based upon the categorical ratings recorded in a patient's daily pain diary over the course of a complete menstrual cycle.

A directed breast examination will be used as a secondary efficacy endpoint. Changes in the brest examination will be determined by the physician after consideration of both the nature of the examination findings and the surface area of breast involvement. Changes as noted after six months of therapy, relative to the screening visit (baseline) will be used to evaluate this endpoint.

Eligibility criteria: Inclusion Criteria:

* History of clinical breast pain.
* Documentation of 6 or more sequential days of moderate or severe pain by patient daily diary.
* Conservative measures such as local heat, non-prescription analgesics, and properly fitted garments are not effective for the treatment of symptoms
* Euthyroid with no prior history of thyroid disease.
* Premenopausal female between the ages of 18 and 50.
* The presence of at least one palpable structure (nodules, cysts) and involvement (diffuse nodularity or breast thickening) of at least 25% of at least one breast surface.

Exclusion Criteria:

* History of thyroid disease
* Non-cyclic breast pain
* Treatment with gonadotropin releasing hormone (GnRH) agonist, Danocrine, tamoxifen, raloxifene, or bromocriptine within three months of starting the trial
* Initiation or change of any hormonal therapy within 6 months of enrollment; including birth control pills, hormone replacement therapy, any progestin including Norplant or Depo-Provera;
* Current treatment with iodine or iodine-containing medications or diagnostics
* Known hypersensitivity to iodine-containing products
* Breast implants;
* Oophorectomy (complete or partial)
* Uncontrolled hypertension;
* Breast biopsy breast biopsy within two months of screening; or expectation of a breast biopsy during the study for a suspicious mass present at baseline;
* Pregnant women or nursing mothers
* History of malignancy within the previous 5 years other than basal cell or squamous cell carcinoma of the skin
* History of breast cancer

Primary outcomes:
measure: Total clinical breast pain as documented by patient daily diary.
Secondary outcomes:
measure: Change in fibrosis based upon breast examination.
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Medical Affiliated Research Center, Inc.
state: Alabama
city: Phoenix
country: United States
facility: Women's Health Research
state: Arizona
city: Tucson
country: United States
facility: Visions Clinical Research
state: Arizona
city: Colorado Springs
country: United States
facility: Expresscare Clinical Research
state: Colorado
city: Denver
country: United States
facility: Downtown Women's Heath Care
state: Colorado
city: Denver
country: United States
facility: University of Colorado
state: Colorado
city: Hartford
country: United States
facility: S.H.E. Medical Associates
state: Connecticut
city: Waterbury
country: United States
facility: The GYN's Center for Women's Health
state: Connecticut
city: West Hartford
country: United States
facility: Greater Hartford Women's Health Associates
state: Connecticut
city: Boynton Beach
country: United States
facility: Visions Clinical Research
state: Florida
city: Clearwater
country: United States
facility: Women's Medical Research Group, LLC
state: Florida
city: Miami
country: United States
facility: Miami Research Associates, Inc.
state: Florida
city: West Palm Beach
country: United States
facility: Palm Beach Research Center
state: Florida
city: Decatur
country: United States
facility: Soapstone Center for Clinical Research
state: Georgia
city: Savannah
country: United States
facility: Fellows Research Alliance, Inc.
state: Georgia
city: Champaign
country: United States
facility: Women's Health Practice
state: Illinois
city: Indianapolis
country: United States
facility: Physicians Research Group
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Lexington
country: United States
facility: Kentucky Medical Research Center
state: Kentucky
city: Marrero
country: United States
facility: York Clinical Consulting
state: Louisiana
city: Wellesley
country: United States
facility: MedVadis Research
state: Massachusetts
city: Worcester
country: United States
facility: Fallon Clinic
state: Massachusetts
city: Kansas City
country: United States
facility: University of Missouri
state: Missouri
city: Saint Louis
country: United States
facility: Department of Ob/Gyn - Women's Health University of Saint Louis
state: Missouri
city: Reno
country: United States
facility: The Medical Group of Northern Nevada
state: Nevada
city: Lawrenceville
country: United States
facility: Women's Health Research Center, LLC
state: New Jersey
city: Moorestown
country: United States
facility: Laurel Creek Research Associates
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center/Albert Einstein College of Medicine
state: New York
city: Raleigh
country: United States
facility: Wake Research Associates, LLC
state: North Carolina
city: Cincinnati
country: United States
facility: Radiant Research
state: Ohio
city: Miamisburg
country: United States
facility: HWC Women's Research Center
state: Ohio
city: Norman
country: United States
facility: LION Research
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Hershey
country: United States
facility: Penn State The Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Drexel University College of Medicine
state: Pennsylvania
city: Pawtucket
country: United States
facility: Memorial Hospital of Rhode Island
state: Rhode Island
city: Hilton Head Island
country: United States
facility: Fellows Research Alliance, Inc.
state: South Carolina
city: Seattle
country: United States
facility: Women's Clinical Research Center/North Seattle Women's Group
state: Washington
city: Tacoma
country: United States
facility: Tacoma Women's Specialists
state: Washington
Study officials:
affiliation: Symbollon Pharmaceuticals, Inc.
name: Julia Kazakhin, M.D.
role: STUDY_DIRECTOR
References:
citation: Aceves C, Anguiano B, Delgado G. Is iodine a gatekeeper of the integrity of the mammary gland? J Mammary Gland Biol Neoplasia. 2005 Apr;10(2):189-96. doi: 10.1007/s10911-005-5401-5.
citation: Cann SA, van Netten JP, van Netten C. Hypothesis: iodine, selenium and the development of breast cancer. Cancer Causes Control. 2000 Feb;11(2):121-7. doi: 10.1023/a:1008925301459.
citation: Kessler JH. The effect of supraphysiologic levels of iodine on patients with cyclic mastalgia. Breast J. 2004 Jul-Aug;10(4):328-36. doi: 10.1111/j.1075-122X.2004.21341.x.
citation: Ghent WR, Eskin BA, Low DA, Hill LP. Iodine replacement in fibrocystic disease of the breast. Can J Surg. 1993 Oct;36(5):453-60.
citation: Garcia-Solis P, Alfaro Y, Anguiano B, Delgado G, Guzman RC, Nandi S, Diaz-Munoz M, Vazquez-Martinez O, Aceves C. Inhibition of N-methyl-N-nitrosourea-induced mammary carcinogenesis by molecular iodine (I2) but not by iodide (I-) treatment Evidence that I2 prevents cancer promotion. Mol Cell Endocrinol. 2005 May 31;236(1-2):49-57. doi: 10.1016/j.mce.2005.03.001. Epub 2005 Apr 13.
citation: Eskin BA, Grotkowski CE, Connolly CP, Ghent WR. Different tissue responses for iodine and iodide in rat thyroid and mammary glands. Biol Trace Elem Res. 1995 Jul;49(1):9-19. doi: 10.1007/BF02788999.
citation: Thrall KD, Bull RJ, Sauer RL. Distribution of iodine into blood components of the Sprague-Dawley rat differs with the chemical form administered. J Toxicol Environ Health. 1992 Nov;37(3):443-9. doi: 10.1080/15287399209531682.
citation: Venturi S. Is there a role for iodine in breast diseases? Breast. 2001 Oct;10(5):379-82. doi: 10.1054/brst.2000.0267.
citation: Smyth PP. Role of iodine in antioxidant defence in thyroid and breast disease. Biofactors. 2003;19(3-4):121-30. doi: 10.1002/biof.5520190304.
citation: Ader DN, South-Paul J, Adera T, Deuster PA. Cyclical mastalgia: prevalence and associated health and behavioral factors. J Psychosom Obstet Gynaecol. 2001 Jun;22(2):71-6. doi: 10.3109/01674820109049956.
citation: Ader DN, Shriver CD, Browne MW. Cyclical mastalgia: premenstrual syndrome or recurrent pain disorder? J Psychosom Obstet Gynaecol. 1999 Dec;20(4):198-202. doi: 10.3109/01674829909075596.
citation: Ader DN, Browne MW. Prevalence and impact of cyclic mastalgia in a United States clinic-based sample. Am J Obstet Gynecol. 1997 Jul;177(1):126-32. doi: 10.1016/s0002-9378(97)70450-2.