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

This study has been terminated.
(Two of 7 subjects' psoriasis worsened on B vitmains and one who improved developed Left axis deviation on EKG)
Sponsor:
Collaborator:
Abbott
Information provided by (Responsible Party):
Peter J. Aronson, MD, Wayne State University
ClinicalTrials.gov Identifier:
NCT01704599
First received: October 3, 2012
Last updated: May 11, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Psoriasis
Drug: Humira Then Humira plus 3 B vitamins
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Wayne State University:

Primary Outcome Measures:
  • PASI [ Time Frame: Change between week 16 on Humira and then after another 12 weeks on Humira plus vitamins ] [ Designated as safety issue: No ]
    The investigators will measure patients' Psoriasis Area and Severity Index (PASI). The PASI assessment includes grading psoriatic involvement (6 point scale), and severity of lesions on the head, trunk, and, upper and lower extremities. PASI scores range from 0.0 to 72.0 (0.1 increments), with a score of 72.0 representing complete erythroderma of the severest possible degree, and a PASI score of 0.0 indicating no psoriatic lesions at all.


Secondary Outcome Measures:
  • PGA [ Time Frame: Change between week 16 on Humira and after another 12 weeks on Humira plus vitamins ] [ Designated as safety issue: No ]
    Physician Global Assessment of Psoriasis (PGA): PGA is a numeric scale which is completed by the physician and is designed to evaluate the physician's overall assessment of the subject's psoriasis based on severity of symptoms. The BSA numerical score will be used to measure the physician's assessment of the proportion of the subject's total BSA involved with psoriasis.

  • DLQI [ Time Frame: Change between week 16 on Humira and then after another 12 weeks on Humira plus vitamins ] [ Designated as safety issue: Yes ]
    Dermatology Life Quality Index (DLQI): DLQI is a self-administered 10-question validated questionnaire that examines the impact of skin disease on quality of life.42 There are 10 questions focusing on the following domains: (1) symptoms & feelings (2) daily activities (3) leisure (4) work & school (5) personal relationship (6) treatment.42 The DLQI, although meant to examine overall skin-related QoL, primarily focuses on social interaction (i.e. shopping, sport, work). Only 2 questions, one regarding physical discomfort and the other regarding treatment, do not directly pertain to social activities.


Other Outcome Measures:
  • Adverse Event [ Time Frame: From Week 0 through day 70 post Week 28 of therapy with first Humira then Humira plus B Vitamins ] [ Designated as safety issue: Yes ]

    An adverse event (AE) is any reaction, side effect, or other untoward medical occurrence, regardless of the relationship to study drug, which occurs at any time during this study after the subject has taken the first dose of study drug. Clinically significant adverse changes in clinical status, x-rays, physical examinations, etc. are considered adverse events. A laboratory abnormality that is associated with signs/symptoms or a diagnosis, or that requires a therapeutic intervention (including dose reduction or discontinuation of the study drug) will be considered as an adverse event.

    Reporting

    All adverse events, whether ascertained through subject interviews, physical examination, laboratory findings, or other means will be recorded separately on an adverse event report form and be conveyed all investigators and sub-investigators via Quartely Data Safety Report and as soon as possible to Abbott.


  • Serious Adverse Event (SAE) [ Time Frame: From Week 0 through day 70 post Week 28 of therapy with first Humira then Humira plus B Vitamins ] [ Designated as safety issue: Yes ]

    A SAE is any adverse event occurring at any dose that results in:

    1. Death
    2. Life-threatening
    3. In-patient hospitalization or prolongation of existing hospitalization
    4. Persistent or significant disability or incapacity
    5. Congenital abnormality or birth defect Any other event thought by the Investigator to be serious should also be reported.

    All encounters are to be copied and sent to the ENTIRE investigating team within one week or sooner (Abbott within 48 hours). In addition, Quarterly reports of all encounters will be summarized and sent to the Wayne State HIC and including Abbott Medical Affairs for Discussion if any aberrant or abnormal results are found that quarter.

    Expedited safety reports (IND Safety Reports)will be sent to the FDA and other regulatory agencies as necessary, and will inform the Investigators of such regulatory reports. Investigators must submit safety reports as required by the Wayne State IRB.


  • Electrocardiogram (EKG) [ Time Frame: At Screening, Week 16 on Humira, Week 28 after another 12 weeks on Humira plus vitamins and if early termination ] [ Designated as safety issue: Yes ]
    A 12 lead electrocardiogram will be taken

  • Plasma VEGF (vascular endothelial growth factor level) [ Time Frame: At Screening visit, Week 16 on Humira, after anotehr 12 weeks on Humira plus vitamins and if early termination ] [ Designated as safety issue: Yes ]
    Blood test requiring venipuncture (if 140 pg/ml or more at screening candidate will not be enrolled)

  • Complete blood count with differential [ Time Frame: At Week 0 just before Humira, Week 16 on Humira, Week 28 after another 12 weeks on Humira plus vitamins and if early termination ] [ Designated as safety issue: Yes ]
    Blood test requiring venipuncture.

  • Serum Magnesium [ Time Frame: At Week 0 just before Humira, Week 16 on Humira, Week 28 after another 12 weeks on Humira plus vitamins and if early termination ] [ Designated as safety issue: Yes ]
    Blood test requiring venipuncture.

  • serum phosphorus [ Time Frame: At Week 0 just before Humira, Week 16 on Humira, Week 28 after another 12 weeks on Humira plus vitamins and if early termination ] [ Designated as safety issue: Yes ]
    Blood test requiring venipuncture.

  • serum homocysteine [ Time Frame: At Week 0 just before Humira, Week 16 on Humira, Week 28 after another 12 weeks on Humira plus vitamins and if early termination ] [ Designated as safety issue: Yes ]
    Blood test requiring venipuncture.

  • Vitamin B12 blood level [ Time Frame: At Week 0 just before Humira, Week 16 on Humira, Week 28 after another 12 weeks on Humira plus vitamins and if early termination ] [ Designated as safety issue: Yes ]
    Blood test requiring venipuncture

  • Vitamin B6 level [ Time Frame: At Week 0 just before Humira, Week 16 on Humira, Week 28 after another 12 weeks on Humira plus vitamins and if early termination ] [ Designated as safety issue: No ]
    Blood test requiring venipuncture

  • Serum folic acid level [ Time Frame: At Week 0 just before Humira, Week 16 on Humira, Week 28 after another 12 weeks on Humira plus vitamins and if early termination ] [ Designated as safety issue: No ]
    Blood test requiring venipuncture

  • Helicobacter pylori antibody [ Time Frame: Week 0 justbefore Humira, Week 28 after 16 weeks of Humira then 12 of Humir-Vitamins ] [ Designated as safety issue: No ]
    Blood test requiring venipuncture.

  • Urine Pregnancy [ Time Frame: At screening, Week 28 after 16 weeks Humira and anotehr 12 of Humira-vitamins ] [ Designated as safety issue: Yes ]
    Urine test (if positive at screening candidae will not be enrolled).

  • Blood Pressure and pulse [ Time Frame: At Week 0, week 16 on Humira, anotehr 12 weeks on Humira plus vitamins and if early termination ] [ Designated as safety issue: Yes ]
    Measaurement using blood pressure cuff with pulse reader

  • Temperature [ Time Frame: At Week 0, week 16 on Humira, anotehr 12 weeks on Humira plus vitamins and if early termination ] [ Designated as safety issue: Yes ]
    Using a thermometer

  • Height [ Time Frame: Week 0 at Start of Humira ] [ Designated as safety issue: Yes ]
    Using ruler

  • Weight [ Time Frame: At Week 0 at start of Humira ] [ Designated as safety issue: Yes ]
    Using scale


Enrollment: 8
Study Start Date: January 2009
Study Completion Date: May 2014
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.

Drug: 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 cycnocobalamin
Other Names:
  • Humira
  • Adalimumab
  • Vitamin B6
  • Pyridoxine
  • Vitamin B9
  • Folic Acid
  • Vitamin B12
  • Cyanocobalamin

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.

Adalimumab is indicated by the Food and Drug Administration (FDA) for the treatment of adults with moderate to severe long standing (chronic) plaque psoriasis. Adalimumab is a medicine called a TNF-alpha (tumor necrosis factor alpha) blocker. The extra TNF-alpha in the body can attack normal healthy body tissues and cause inflammation. The purposes of this study are to investigate the effects of the addition of 12 weeks of modulators of homocysteine (oral vitamin B12, oral vitamin B6 or pyridoxine, and oral folic acid) plus adalimumab after 16 weeks adalimumab therapy on the clinical appearance of psoriasis and on laboratory values correlated with the use and disuse of said modulators. Given that near maximum clinical improvement on adalimumab is expected after 16 weeks of adalimumab, if further clearcut improvement was seen in most subjects at the 28 week visit, it would be attributed to the addition of the vitamins.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01704599

Locations
United States, Michigan
Wayne State University Physician Group Dermatology
Dearborn, Michigan, United States, 48124
Sponsors and Collaborators
Wayne State University
Abbott
Investigators
Principal Investigator: Peter J Aronson, MD Department Dermatology Wayne State University
  More Information

Additional Information:
Humira  This link exits the ClinicalTrials.gov site

Publications:

Responsible Party: Peter J. Aronson, MD, Assistant Professor Department of Dermatology, Wayne State University
ClinicalTrials.gov Identifier: NCT01704599     History of Changes
Other Study ID Numbers: Dermatology 1104009591
Study First Received: October 3, 2012
Last Updated: May 11, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Wayne State University:
Psoriasis
Adalimumab
B vitamins
Homocysteine
Folic acid
Cyanocobalamin
Pyridoxine
Vitamin B6
Vitamin B9
Vitamin B12

Additional relevant MeSH terms:
Psoriasis
Skin Diseases
Skin Diseases, Papulosquamous
Adalimumab
Folic Acid
Hydroxocobalamin
Pyridoxal
Pyridoxine
Vitamin B 12
Vitamin B 6
Vitamin B Complex
Vitamins
Anti-Inflammatory Agents
Antirheumatic Agents
Growth Substances
Hematinics
Hematologic Agents
Micronutrients
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014