Vitamin D Deficiency Causes Immune Dysfunction and Enables or Perpetuates the Development of Rheumatoid Arthritis

NCT00279461 | Withdrawn Phase 2

• 2 other identifiers: 21562No secondary ID at this time
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Recent studies have demonstrated that subjects with low blood levels of vitamin D are at a higher risk of developing autoimmune diseases such as Rheumatoid Arthritis (RA). We are pursuing these studies to test the hypothesis that restoration of vitamin D levels ameliorates the manifestations of RA. We will test this hypothesis by inviting patients with RA to participate in a trial that examines the effects of oral vitamin D administration on the clinical expression of this disease. For this purpose, the participants of this trial will be asked to take an oral dose of 2,000 units of vitamin D daily for 6 months. We will examine the participant's joints, assess disease activity measures, and determine his/her blood levels of vitamin D before starting this treatment and periodically thereafter.

Conditions

Arthritis, Rheumatoid; Vitamin D Deficiency

Keywords

Rheumatoid Arthritis; Vitamin D

Outcome Measures

Primary Outcomes (1)

• ACR20

  Baseline and every 2 months for 6 months

Secondary Outcomes (1)

• Changes in surface marker expression of blood myeloid dendritic cells

  Baseline and at completion of study on the 6th month

Study Arms (2)

A,

EXPERIMENTAL

Arm A: Vitamin D 2,000 units daily all in one capsule for 6 months

Drug: Placebo in arm A and Vitamin D in arm B

B

PLACEBO COMPARATOR

Arm B: matching placebo one capsule daily for 6 months

Drug: vitamin D 3 for arm A ,and matching placebo for arm B

Interventions

Placebo in arm A and Vitamin D in arm B DRUG

Vitamin D3 at 2,000 units daily, all in one capsule, for 6 months and Placebo provided in matching capsule, one capsule daily, for 6 months

Also known as: Vitamin D3 is also called cholecalciferol

A,

vitamin D 3 for arm A ,and matching placebo for arm B DRUG

Arm A 2,000 units of Vitamin D3 in one capsule daily for 6 months. Arm B matching placebo capsule, one daily for 6 months

Also known as: Cholecalciferol

B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• This study will involve two groups of patients fulfilling the following eligibility requirements:
• they should have early (not more than 12 month duration) active RA as determined by the diagnostic criteria and active status definitions as described below, and
• All RA patients in this study will satisfy the American Rheumatism Association 1987 revised criteria for the diagnosis of RA. Active disease will be defined by the presence of at least 3 swollen joints, ≥6 tender or painful joints and at least 2 of the following features: duration of morning stiffness 60 minutes, erythrocyte sedimentation rate (ESR) ≥28 mm/hour and serum CRP level of at least 2.0 mg/dl (26).
• Only research subjects of either gender who are 18 years of age or older will be invited to participate.

You may not qualify if:

• To minimize the impact of pre-existing treatments on the final outcome of this trial, patients taking NSAIDs and/or prednisone will be required to receive unchanged doses of these medications for at least 1 month. No modifications of these treatments will be allowed during the study. In addition to their methotrexate treatment, patients within Group A will receive placebo every day for 12 consecutive months.
• The second group, Group B, will include those patients as described for Group A who instead of placebo will receive oral vitamin D, 1,000 units every day for 12 consecutive months added to their standard RA treatment.
• Because cancer and other autoimmune diseases may be more frequent in individuals with a moderate deficiency of vitamin D, subjects with a history of these conditions will be excluded. Because of the remote possibility of vitamin D-induced hypercalcemia, we are aiming at recruiting patients with RA who are otherwise healthy. We will exclude patients who in the past had or currently have cancer (except if considered cured), kidney stones, chronic renal failure, congestive heart failure, arrythmia requiring treatment with antiarrythmics, pulmonary conditions requiring ambulatory oxygen, abnormal levels of calcium or elevated PTH.
• Patients who use Digoxin (drug interaction), or had experienced angina or myocardial infarction in the last 3 years also will be excluded, but patients whose coronary artery disease has been asymptomatic for at least 3 years and who do not have congestive heart failure will be allowed to participate.
• Patients who develop hypercalcemia, kidney stones, elevation of 25(OH)vitamin D\> 90 ng/ml also will be excluded.

Sponsors & Collaborators

• Indiana University: lead

Study Sites (1)

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Related Publications (3)

• Andjelkovic Z, Vojinovic J, Pejnovic N, Popovic M, Dujic A, Mitrovic D, Pavlica L, Stefanovic D. Disease modifying and immunomodulatory effects of high dose 1 alpha (OH) D3 in rheumatoid arthritis patients. Clin Exp Rheumatol. 1999 Jul-Aug;17(4):453-6.

  PMID: 10464556 BACKGROUND

• Cantorna MT, Hayes CE, DeLuca HF. 1,25-Dihydroxycholecalciferol inhibits the progression of arthritis in murine models of human arthritis. J Nutr. 1998 Jan;128(1):68-72. doi: 10.1093/jn/128.1.68.

  PMID: 9430604 BACKGROUND

• Adorini L, Penna G, Giarratana N, Roncari A, Amuchastegui S, Daniel KC, Uskokovic M. Dendritic cells as key targets for immunomodulation by Vitamin D receptor ligands. J Steroid Biochem Mol Biol. 2004 May;89-90(1-5):437-41. doi: 10.1016/j.jsbmb.2004.03.013.

  PMID: 15225816 BACKGROUND

MeSH Terms

Conditions

Arthritis, Rheumatoid; Vitamin D Deficiency

Interventions

Vitamin D; Cholecalciferol

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Secosteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Cholestenes; Cholestanes; Sterols; Membrane Lipids; Lipids

Study Officials

• Ernesto N Levy, MD

  India na University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: January 17, 2006
• First Posted: January 19, 2006
• Study Start: May 1, 2009
• Primary Completion: May 1, 2011
• Study Completion: May 1, 2011
• Last Updated: August 4, 2015

Record last verified: 2015-07

Locations

US (1)