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

Information source: Wayne State University
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Psoriasis

Intervention: Humira Then Humira plus 3 B vitamins (Drug)

Phase: Phase 1/Phase 2

Status: Terminated

Sponsored by: Wayne State University

Official(s) and/or principal investigator(s):
Peter J Aronson, MD, Principal Investigator, Affiliation: Department Dermatology Wayne State University

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.

Clinical Details

Official title: A Single-Center, Open-Label Study to Assess the Effects of the Addition of Modulators of Homocysteine to Adalimumab Therapy in the Treatment of Moderate to Severe Plaque Psoriasis Evaluated With the PASI, PGA and DLQI

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Number of Particpants With a Categorical PASI (Psoriasis Area and Severity Index) Change

Secondary outcome:

Number of Participants With a Categorical Change in Static Physician Global Assessment (sPGA):

Number of Participants With a Categorical DLQI (Dermatology Life Quality Index) Change

Number of Participants With Category Change in Serum VEGF (Vascular Endothelial Growth Factorl)

Number of Participants Within the Categories of Increasing and Decreasing Serum Homocysteine

Number of Participants With Category Change in Vitamin B12 Blood Level

Number of Participants Within the Categories of Increasing and Decreasing Serum Vitamin B6 Level

Number of Participants With Category Change in Serum Folic Acid Level.

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.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

Locations and Contacts

Additional Information

Search for Humira

Humira

hypermagnesemia

Related publications:

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.

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.

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.

Lewis V, Finlay AY. 10 years experience of the Dermatology Life Quality Index (DLQI). J Investig Dermatol Symp Proc. 2004 Mar;9(2):169-80. Review.

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. Epub 2006 Aug 10.

Genovese MC, Mease PJ, Thomson GT, Kivitz AJ, Perdok RJ, Weinberg MA, Medich J, Sasso EH; M02-570 Study Group. Safety and efficacy of adalimumab in treatment of patients with psoriatic arthritis who had failed disease modifying antirheumatic drug therapy. J Rheumatol. 2007 May;34(5):1040-50. Epub 2007 Apr 15. Erratum in: J Rheumatol. 2007 Jun;34(6):1439.

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.

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.

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.

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.

Suárez-Fariñas 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.

Starting date: January 2009
Last updated: January 30, 2015

Page last updated: August 23, 2015

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