3,3'-Diindolylmethane in Patients With Systemic Lupus Erythematosus

NCT02483624 | Terminated Phase 1 DMC

• 1 other identifier: 06.02.107T
• Study Type: interventional
• Target: 6
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a single center study of patients with inactive or mild SLE being performed to determine the safety, tolerability, and pharmacodynamics of DIM.

Conditions

SLE

Outcome Measures

Primary Outcomes (4)

• Safety and Tolerability Routine clinical and laboratory parameters as well as SLE activity measurement with SELENA Systemic Lupus Erythematosus Disease Activity Index assessment.

  Routine clinical and laboratory parameters as well as SLE activity measurement with SELENA Systemic Lupus Erythematosus Disease Activity Index assessment.

  14 months

• Estradiol Hydroxylation Pathways

  Measure alterations in the ratio of 2-hydroxyestrone/ 16alpha-hydroxyestrone (2-OHE/16alpha-OHE) in the urine.

  14 months

• Autoantibody Production

  Routine lab testing to determine whether DIM supplementation will decrease autoantibody production

  14 Months

• T and B Lymphocytes

  Qualitative and quantitative abnormalities in B- and T-lymphocytes abound in human SLE. In this aim, phenotypic analyses of B- and T-lymphocyte subsets as well as functional analyses will be ascertained in order to evaluate the effects of DIM on these parameters.

  14 Months

Study Arms (3)

Low Dose

EXPERIMENTAL

10 patients 225 mg of BR-DIM. 2 capsules AM and 1 PM. 52 weeks duration.

Drug: BR-DIM

High Dose

EXPERIMENTAL

10 patients 375 mg of BR-DIM. 3 capsules AM and 2 PM. 52 weeks duration.

Drug: BR-DIM

Placebo

PLACEBO COMPARATOR

10 patients receiving weight matched placebo. 5 for high dose and 5 for low dose. 52 weeks of weight matched pills.

Drug: Placebo

Interventions

BR-DIM DRUG

DIM, a condensation product of indole-3-carbinol (IC3), is a phytochemical that has activity against certain tumor cells. Observations in lupus-prone mice treated with indole-3-carbinol suggest that DIM might have favorable biologic and clinical effects in human SLE.

Also known as: 3,3'-diindolylmethane

High Dose; Low Dose

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Stable SLE disease activity for a period of at least 2 months prior to the Screening visit, based on the clinical judgment of the investigators
• History of measurable anti-dsDNA, anti-Sm, RNP, SS-A (anti-Ro), or SS-B (anti-La) autoantibodies
• Age \> 18 and \< 50
• Ability to understand the requirements of the study, provide written consent, and comply with the study protocol procedures
• A negative pregnancy test
• The use of contraception by fertile females
• A serum creatinine \<1.8 mg/dL
• Serum hepatic transaminases \< 1.25 times the upper limits of normal
• Hemoglobin \> 9.5, WBC \> 3.0, neutrophils \> 1.2; platelets \> 90,000

You may not qualify if:

• Immunosuppressive therapy (e.g. cyclophosphamide, cyclosporine, azathioprine, mycophenolate mofetil) or intravenous gamma globulin within 6 months of study entry
• Prior receipt of biologic agents, unless 9 months or 4 half-lives, whichever is greater, have passed since the last dose
• Prednisone \> 10 mg/day (or its pharmacologic equivalent) within 2 months of randomization
• Pregnancy or the intent to conceive during the study or 3 months after study completion
• Concurrent medications such as danazol, DHEA, or other medications that affect estrogen levels or metabolism
• Nursing mothers
• Oral contraceptive use
• The presence of infection
• A history of poor procedural compliance
• Receipt of an investigational drug within 60 days of baseline
• Malignancy (except for basal cell carcinoma)
• Dose changes of steroids, anti-malarial drugs, or NSAID's within 4 weeks of randomization
• Peri- or post-menopausal state
• History of clinical evidence of active significant acute or chronic diseases (i.e., cardiovascular, pulmonary, untreated hypertension, anemia, gastrointestinal, hepatic, renal, neurological, cancer, or infectious diseases) that could confound the results of the study or put the subject at undue risk
• History of any other medical disease, laboratory abnormalities, or conditions that would make the subject (in the opinion of the investigators) unsuitable for the study

Sponsors & Collaborators

• Northwell Health: lead

Related Publications (17)

• Roubinian JR, Talal N, Greenspan JS, Goodman JR, Siiteri PK. Effect of castration and sex hormone treatment on survival, anti-nucleic acid antibodies, and glomerulonephritis in NZB/NZW F1 mice. J Exp Med. 1978 Jun 1;147(6):1568-83. doi: 10.1084/jem.147.6.1568.

  PMID: 308087 BACKGROUND

• Roubinian J, Talal N, Siiteri PK, Sadakian JA. Sex hormone modulation of autoimmunity in NZB/NZW mice. Arthritis Rheum. 1979 Nov;22(11):1162-9. doi: 10.1002/art.1780221102. No abstract available.

  PMID: 508370 BACKGROUND

• Carlsten H, Nilsson N, Jonsson R, Backman K, Holmdahl R, Tarkowski A. Estrogen accelerates immune complex glomerulonephritis but ameliorates T cell-mediated vasculitis and sialadenitis in autoimmune MRL lpr/lpr mice. Cell Immunol. 1992 Oct 1;144(1):190-202. doi: 10.1016/0008-8749(92)90236-i.

  PMID: 1394437 BACKGROUND

• Petri M. Exogenous estrogen in systemic lupus erythematosus: oral contraceptives and hormone replacement therapy. Lupus. 2001;10(3):222-6. doi: 10.1191/096120301676707393.

  PMID: 11315357 BACKGROUND

• Bradlow HL, Telang NT, Sepkovic DW, Osborne MP. 2-hydroxyestrone: the 'good' estrogen. J Endocrinol. 1996 Sep;150 Suppl:S259-65.

  PMID: 8943806 BACKGROUND

• Swaneck GE, Fishman J. Covalent binding of the endogenous estrogen 16 alpha-hydroxyestrone to estradiol receptor in human breast cancer cells: characterization and intranuclear localization. Proc Natl Acad Sci U S A. 1988 Nov;85(21):7831-5. doi: 10.1073/pnas.85.21.7831.

  PMID: 3186693 BACKGROUND

• Lahita RG, Bradlow HL, Kunkel HG, Fishman J. Increased 16 alpha-hydroxylation of estradiol in systemic lupus erythematosus. J Clin Endocrinol Metab. 1981 Jul;53(1):174-8. doi: 10.1210/jcem-53-1-174.

  PMID: 7240374 BACKGROUND

• Michnovicz JJ, Bradlow HL. Altered estrogen metabolism and excretion in humans following consumption of indole-3-carbinol. Nutr Cancer. 1991;16(1):59-66. doi: 10.1080/01635589109514141.

  PMID: 1656396 BACKGROUND

• Bradlow HL, Michnovicz J, Telang NT, Osborne MP. Effects of dietary indole-3-carbinol on estradiol metabolism and spontaneous mammary tumors in mice. Carcinogenesis. 1991 Sep;12(9):1571-4. doi: 10.1093/carcin/12.9.1571.

  PMID: 1893517 BACKGROUND

• Michnovicz JJ, Adlercreutz H, Bradlow HL. Changes in levels of urinary estrogen metabolites after oral indole-3-carbinol treatment in humans. J Natl Cancer Inst. 1997 May 21;89(10):718-23. doi: 10.1093/jnci/89.10.718.

  PMID: 9168187 BACKGROUND

• Chen DZ, Qi M, Auborn KJ, Carter TH. Indole-3-carbinol and diindolylmethane induce apoptosis of human cervical cancer cells and in murine HPV16-transgenic preneoplastic cervical epithelium. J Nutr. 2001 Dec;131(12):3294-302. doi: 10.1093/jn/131.12.3294.

  PMID: 11739883 BACKGROUND

• Rosen CA, Woodson GE, Thompson JW, Hengesteg AP, Bradlow HL. Preliminary results of the use of indole-3-carbinol for recurrent respiratory papillomatosis. Otolaryngol Head Neck Surg. 1998 Jun;118(6):810-5. doi: 10.1016/S0194-5998(98)70274-8.

  PMID: 9627242 BACKGROUND

• Bell MC, Crowley-Nowick P, Bradlow HL, Sepkovic DW, Schmidt-Grimminger D, Howell P, Mayeaux EJ, Tucker A, Turbat-Herrera EA, Mathis JM. Placebo-controlled trial of indole-3-carbinol in the treatment of CIN. Gynecol Oncol. 2000 Aug;78(2):123-9. doi: 10.1006/gyno.2000.5847.

  PMID: 10926790 BACKGROUND

• Auborn KJ, Qi M, Yan XJ, Teichberg S, Chen D, Madaio MP, Chiorazzi N. Lifespan is prolonged in autoimmune-prone (NZB/NZW) F1 mice fed a diet supplemented with indole-3-carbinol. J Nutr. 2003 Nov;133(11):3610-3. doi: 10.1093/jn/133.11.3610.

  PMID: 14608082 BACKGROUND

• Theofilopoulos AN, Dixon FJ. Murine models of systemic lupus erythematosus. Adv Immunol. 1985;37:269-390. doi: 10.1016/s0065-2776(08)60342-9. No abstract available.

  PMID: 3890479 BACKGROUND

• Anderton MJ, Manson MM, Verschoyle R, Gescher A, Steward WP, Williams ML, Mager DE. Physiological modeling of formulated and crystalline 3,3'-diindolylmethane pharmacokinetics following oral administration in mice. Drug Metab Dispos. 2004 Jun;32(6):632-8. doi: 10.1124/dmd.32.6.632.

  PMID: 15155555 BACKGROUND

• Reed GA, Sunega JM, Sullivan DK, Gray JC, Mayo MS, Crowell JA, Hurwitz A. Single-dose pharmacokinetics and tolerability of absorption-enhanced 3,3'-diindolylmethane in healthy subjects. Cancer Epidemiol Biomarkers Prev. 2008 Oct;17(10):2619-24. doi: 10.1158/1055-9965.EPI-08-0520.

  PMID: 18843002 BACKGROUND

MeSH Terms

Interventions

3,3'-diindolylmethane

Study Officials

• Richard Furie, MD

  NorthShore-LIJ Health System

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2015
• First Posted: June 29, 2015
• Study Start: January 1, 2016
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: February 1, 2016

Record last verified: 2016-01