Addition of Modulators of Homocysteine to Adalimumab Therapy in the Treatment of Moderate to Severe Plaque Psoriasis

NCT ID: NCT01704599

Last Updated: 2015-02-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-01-31
• Study Completion Date: 2014-05-31

Brief Summary

Vitamins modulating homocysteine affect both TNF-alpha, vascular endothelial growth factor, and theoretically enhance the anti-inflammatory version of NOS thus hopefully increasing the efficacy and reducing the chance of some toxicities of adalimumab as determined by blood testing and EKGs.

Detailed Description

This is a pilot study designed to evaluate whether addition of oral vitamin B12, vitamin B6, and folic acid to the use of adalimumab for psoriasis leads to further improvement of a patient's psoriasis and quality of life.

Conditions

Psoriasis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Humira then Humira plus 3 B vitamins

Humira then Humira plus 3 B vitamins

The only arm: After 16 weeks on adalimumab, modulators of homocysteine (oral vitamin B12, oral vitamin B6 or pyridoxine, and oral folic acid) will be added to adalimumab therapy for an additional 12 weeks. At end of this therapy can stop or continue. Telephone call day 70 after formal end of in person study the investigators will assess general health of each subject.

Group Type: EXPERIMENTAL

Humira Then Humira plus 3 B vitamins

Intervention Type: DRUG

Humira alone for 16 weeks then Humira plus 100 mg daily pyridoxine, 5 mg daily folic acid and 1000 mcg daily cyanocobalamin

Interventions

Humira Then Humira plus 3 B vitamins

Humira alone for 16 weeks then Humira plus 100 mg daily pyridoxine, 5 mg daily folic acid and 1000 mcg daily cyanocobalamin

Intervention Type: DRUG

Other Intervention Names

Humira; Adalimumab; Vitamin B6; Pyridoxine; Vitamin B9; Folic Acid; Vitamin B12; Cyanocobalamin

Eligibility Criteria

Inclusion Criteria

• adults 18 or older
• moderate to severe plaque psoriasis (>10% BSA)
• Negative pregnancy test within 7 days before first dose of adalimumab in all women (except surgically sterile or 5 years postmenopausal)
• subject must sign/date appropriate written informed consent&HIPAA authorization
• Sexually active subjects of childbearing potential must agree to use medically acceptable contraception during screening and throughout the study
• no evidence of active or latent tuberculosis based on a negative PPD skin test performed at screening, or within one year of starting this study. Patients with documentation of adequately treated TB may be enrolled
• Patients PPD positive and CXR negative can be enrolled if they finish appropriate INH prophylaxis prior to enrollment
• be willing and able to self-administer subcutaneous injections or to have a qualified person available to administer these injections
• agrees to comply with protocol requirements, attend all regularly study visits and is considered to be a good study subject
• meets concomitant medication washout requirements
• willing to use only allowed psoriasis medications and treatments and agree not to start any topical, systemic, or phototherapy for psoriasis during the study period
• adalimumab naïve

Exclusion Criteria

• erythrodermic, pustular, or guttate psoriasis
• skin conditions other than psoriasis that would interfere with study-related psoriasis evaluations
• known sensitivity to any component of the study medications
• Evidence of active infections such as fevers, chills, sweats, or history of untreated Lyme disease and active severe infections within 4 weeks before screening visit, or between the screening and Week 0 visits
• history of listeriosis, untreated TB, persistent or active infections requiring hospitalization or treatment with IV antibiotics, IV antiretrovirals, or IV antifungals within 30 days of baseline, OR oral antibiotics, antivirals, or antifungals for purpose of treating infection, within 14 days of baseline
• positive PPD and positive chest x-ray for latent or active tuberculosis
• positive PPD and negative chest x-ray that have not completed appropriate INH prophylaxis
• On immune compromising drug or history of immune compromising disorder or immunodeficiency
• poorly controlled medical condition including, not limited to, unstable cardiovascular disease, poorly controlled diabetes, recent stroke, history of recurrent infections, or any condition for which, in the opinion of the investigators, participation in the study would place the subject at risk
• hx. congestive heart failure
• hx. demyelinating CNS disease
• History of malignancy (other than previously treated localized carcinoma in situ of the cervix or previously treated nonmelanoma skin cancer)
• history of or ongoing drug or alcohol abuse
• past or present psychiatric morbidity which may compromise the study
• Pregnant women, nursing mothers, or planning to become pregnant during study or within 150 days after last dose of study medication. Males planning pregnancy with spouse/partner while in study are to be excluded
• plans to receive any live vaccines during study
• history of liver disease
• Current enrollment in another clinical study/treatment with other experimental drug or approved therapy for experimental use within 30 days prior to Week 0
• previous enrollment in this study
• cannot commit to all assessments required by the protocol
• disorder that compromises the subject to give written informed consent and/or comply with study procedures
• considered by the investigators to be unsuitable candidate
• cannot comply with the protocol washout requirements
• on folic acid in doses over than the minimal daily requirements
• on vitamins higher than minimal daily requirements (multivitamins are allowed)
• colon polyps or cancer
• prior adalimumab therapy
• on screening plasma Vascular Endothelial Growth Factor level is 140 pg/ml or more

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Abbott

INDUSTRY

Sponsor Role: collaborator

Wayne State University

OTHER

Sponsor Role: lead

Responsible Party

Peter J. Aronson, MD

Assistant Professor Department of Dermatology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Peter J Aronson, MD

Role: PRINCIPAL_INVESTIGATOR

Department Dermatology Wayne State University

References

Aronson PJ, Malick F. Towards rational treatment of severe psoriasis in alcoholics: report of two cases. J Drugs Dermatol. 2010 Apr;9(4):405-8.

Reference Type: BACKGROUND

PMID: 20514802 (View on PubMed)

Moat SJ, Madhavan A, Taylor SY, Payne N, Allen RH, Stabler SP, Goodfellow J, McDowell IF, Lewis MJ, Lang D. High- but not low-dose folic acid improves endothelial function in coronary artery disease. Eur J Clin Invest. 2006 Dec;36(12):850-9. doi: 10.1111/j.1365-2362.2006.01739.x.

Reference Type: BACKGROUND

PMID: 17087779 (View on PubMed)

Li W, Zheng T, Wang J, Altura BT, Altura BM. Extracellular magnesium regulates effects of vitamin B6, B12 and folate on homocysteinemia-induced depletion of intracellular free magnesium ions in canine cerebral vascular smooth muscle cells: possible relationship to [Ca2+]i, atherogenesis and stroke. Neurosci Lett. 1999 Oct 22;274(2):83-6. doi: 10.1016/s0304-3940(99)00683-7.

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Reference Type: BACKGROUND

PMID: 15083785 (View on PubMed)

Gordon KB, Langley RG, Leonardi C, Toth D, Menter MA, Kang S, Heffernan M, Miller B, Hamlin R, Lim L, Zhong J, Hoffman R, Okun MM. Clinical response to adalimumab treatment in patients with moderate to severe psoriasis: double-blind, randomized controlled trial and open-label extension study. J Am Acad Dermatol. 2006 Oct;55(4):598-606. doi: 10.1016/j.jaad.2006.05.027. Epub 2006 Aug 10.

Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Pitarch G, Sanchez-Carazo JL, Mahiques L, Perez-Ferriols MA, Fortea JM. Treatment of psoriasis with adalimumab. Clin Exp Dermatol. 2007 Jan;32(1):18-22. doi: 10.1111/j.1365-2230.2006.02288.x.

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Leonardi C, Langley RG, Papp K, Tyring SK, Wasel N, Vender R, Unnebrink K, Gupta SR, Valdecantos WC, Bagel J. Adalimumab for treatment of moderate to severe chronic plaque psoriasis of the hands and feet: efficacy and safety results from REACH, a randomized, placebo-controlled, double-blind trial. Arch Dermatol. 2011 Apr;147(4):429-36. doi: 10.1001/archdermatol.2010.384. Epub 2010 Dec 20.

Reference Type: BACKGROUND

PMID: 21173304 (View on PubMed)

Stuart PE, Nair RP, Ellinghaus E, Ding J, Tejasvi T, Gudjonsson JE, Li Y, Weidinger S, Eberlein B, Gieger C, Wichmann HE, Kunz M, Ike R, Krueger GG, Bowcock AM, Mrowietz U, Lim HW, Voorhees JJ, Abecasis GR, Weichenthal M, Franke A, Rahman P, Gladman DD, Elder JT. Genome-wide association analysis identifies three psoriasis susceptibility loci. Nat Genet. 2010 Nov;42(11):1000-4. doi: 10.1038/ng.693. Epub 2010 Oct 17.

Reference Type: BACKGROUND

PMID: 20953189 (View on PubMed)

Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and its Panel on Folate, Other B Vitamins, and Choline. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington (DC): National Academies Press (US); 1998. Available from http://www.ncbi.nlm.nih.gov/books/NBK114310/

Reference Type: BACKGROUND

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Suarez-Farinas M, Fuentes-Duculan J, Lowes MA, Krueger JG. Resolved psoriasis lesions retain expression of a subset of disease-related genes. J Invest Dermatol. 2011 Feb;131(2):391-400. doi: 10.1038/jid.2010.280. Epub 2010 Sep 23.

Reference Type: BACKGROUND

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Related Links

http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails

Search for Humira

http://www.emedicine.com/med/topic3383.htm

hypermagnesemia

Other Identifiers

Dermatology 1104009591

Identifier Type: -

Identifier Source: org_study_id