Arthritis, RheumatoidPhase 2NCT00279461
Vitamin D Deficiency Causes Immune Dysfunction and Enables or Perpetuates the Development of Rheumatoid Arthritis
A Phase 2 study of Arthritis, Rheumatoid and Vitamin D Deficiency, run by Indiana University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Arthritis, Rheumatoid, Vitamin D Deficiency
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- May 2009to May 2011
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- they should have at the time of inclusion a 25(OH)vitamin D level below 30 ng/ml.
- 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.
- One group, Group A, will include active RA patients receiving treatment with methotrexate. A concomitant prescription of non-steroidal anti-inflammatory drugs (NSAIDs), and/or Prednisone ≤ 10 mg/day will be allowed. Treatment with anti-TNF agents, Abatacept or other immunosuppressives constitute exclusion criteria.
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Vitamin D Deficiency Causes Immune Dysfunction and Enables or Perpetuates the Development of Rheumatoid Arthritis: Clinical Trial and Investigations on Dendritic Cells
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.
Read the detailed description
Rationale : Low vitamin D levels hinders the ability of the macrophage to produce activated 1-25Dihydroxyvitamin at sites of inflammation. 1-25Dihydroxyvitamin D has important immunoregulatory functions including down-regulation of antigen-presenting cells such as dendritic cells. Under the influence of 1-25Dihydroxyvitamin D, these dendritic cells become tolerogenic - as opposed to immunogenic - and abrogate an immune response at early stages. Immunogenic dendritic cells play a key role in the development of autoimmune diseases such as Rheumatoid Arthritis (RA) by "presenting" self-antigens to the immune system. Vitamin D levels are frequently low in patients with RA. Restoring vitamin D availability to normal levels in patients with RA may induce improvement of disease manifestations through expansion of the tolerogenic dendritic cell subset.
Key Objectives:
- Conduct a double-blind randomized clinical trial, to test the hypothesis that vitamin D administered to patients with active RA has beneficial effects on this disease.
- Determine if vitamin D administered to patients with RA. induces expansion of the tolerogenic dendritic cell subset by analyzing patterns of cell surface marker expression on dendritic cells at different time points during the clinical trial (translational studies).
Study Population: We will recruit early RA patients (not more that 12 month duration of disease)with active joint inflammation cared for at this institution.Participants must be subjects with active RA at the time of inclusion, who are 18 years of age or older and have no history of other autoimmune disorders or other disorders such as cancer or osteoporosis which are also linked to vitamin D deficiency. The eligible patients with active RA should be on treatment for RA with Methotrexate at the time of inclusion. Patients taking anti-cytokine treatments (considered not standard) would be excluded. Other exclusions include hypercalcemia, and a history of renal failure or renal stones.
20-25 participants will be allocated to the Vitamin D Group, Arm A. 20-25 participants will be allocated to Placebo Group Arm B Allocation will be conducted in a randomized, double-blind fashion.
Summary of Procedures : After signing a written consent, all potential candidates will undergo a screening interview with the PI and screening blood tests (a blood sample of 20 ml is required).
RA subjects who qualify to receive the study treatment will be randomized to receive oral vitamin D 2,000 units or placebo daily for 6 months. Patients will be examined on a monthly basis and will be drawn a 20 ml blood sample every 2 months for monitoring purposes for a period of 12 month. The participants within the clinical trial who also participate in the translational studies on dendritic cells, will be drawn an additional blood sample of 40 ml on the first month and at the end of the study to isolate their blood dendritic cells. We will study the expression of different activation markers on dendritic cells from consenting participants using various immunologic techniques. This will allow us to identify and quantify the tolerogenic dendritic cells..
- Conditions
- Arthritis, Rheumatoid, Vitamin D Deficiency
- Being tested
- Placebo in arm A and Vitamin D in arm B, vitamin D 3 for arm A ,and matching placebo for arm B
- Keywords
- Rheumatoid Arthritis, Vitamin D
- Medical subject headings
- Arthritis, Rheumatoid, Vitamin D Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Placebo in arm A and Vitamin D in arm BDrug
Also called Vitamin D3 is also called cholecalciferol
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
vitamin D 3 for arm A ,and matching placebo for arm BDrug
Also called Cholecalciferol
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
| Study group | Role | What they receive |
|---|---|---|
| A, | Experimental | Arm A: Vitamin D 2,000 units daily all in one capsule for 6 months Receives: Drug: Placebo in arm A and Vitamin D in arm B |
| B | Placebo comparator | Arm B: matching placebo one capsule daily for 6 months Receives: Drug: vitamin D 3 for arm A ,and matching placebo for arm B |
What is being measured
The primary outcome is the main question the study is designed to answer.
ACR20
Measured: Baseline and every 2 months for 6 months
Secondary outcomes (1)
Changes in surface marker expression of blood myeloid dendritic cells
Measured: Baseline and at completion of study on the 6th month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jan 2006 (estimated)
- Study startMay 2009
- Primary completionMay 2011 (estimated)
- Study completionMay 2011 (estimated)
Why it stopped: Dr. Levy terminated from IU in December 2009. Indiana University has no record that this study was initiated prior to his termination.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Arthritis, RheumatoidStudies of the same condition, open and under way.
- More trials run by Indiana UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Investigators
- Ernesto N Levy, MD, Principal investigator, India na University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00279461
- Sponsor's protocol ID
- 21562
- Other IDs
- No secondary ID at this time
- Status last verified
- Jul 2015
- First submitted
- 17 Jan 2006
- Last updated
- 4 Aug 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 10464556Cantorna 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.
PubMed 9430604Adorini 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.
PubMed 15225816
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vitamin D Deficiency Causes Immune Dysfunction and Enables or Perpetuates the Development of Rheumatoid Arthritis: Clinical Trial and Investigations on Dendritic Cells
- ClinicalTrials.gov ID
- NCT00279461
- Acronym / sponsor ID
- 21562
- Conditions
- Arthritis, Rheumatoid, Vitamin D Deficiency
- Keywords
- Rheumatoid Arthritis, Vitamin D
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Dr. Levy terminated from IU in December 2009. Indiana University has no record that this study was initiated prior to his termination.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Study start
- May 2009
- Primary completion
- May 2011 (estimated)
- Study completion
- May 2011 (estimated)
- First posted
- 19 Jan 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Rationale : Low vitamin D levels hinders the ability of the macrophage to produce activated 1-25Dihydroxyvitamin at sites of inflammation. 1-25Dihydroxyvitamin D has important immunoregulatory functions including down-regulation of antigen-presenting cells such as dendritic cells. Under the influence of 1-25Dihydroxyvitamin D, these dendritic cells become tolerogenic - as opposed to immunogenic - and abrogate an immune response at early stages. Immunogenic dendritic cells play a key role in the development of autoimmune diseases such as Rheumatoid Arthritis (RA) by "presenting" self-antigens to the immune system. Vitamin D levels are frequently low in patients with RA. Restoring vitamin D availability to normal levels in patients with RA may induce improvement of disease manifestations through expansion of the tolerogenic dendritic cell subset.
Key Objectives:
- Conduct a double-blind randomized clinical trial, to test the hypothesis that vitamin D administered to patients with active RA has beneficial effects on this disease.
- Determine if vitamin D administered to patients with RA. induces expansion of the tolerogenic dendritic cell subset by analyzing patterns of cell surface marker expression on dendritic cells at different time points during the clinical trial (translational studies).
Study Population: We will recruit early RA patients (not more that 12 month duration of disease)with active joint inflammation cared for at this institution.Participants must be subjects with active RA at the time of inclusion, who are 18 years of age or older and have no history of other autoimmune disorders or other disorders such as cancer or osteoporosis which are also linked to vitamin D deficiency. The eligible patients with active RA should be on treatment for RA with Methotrexate at the time of inclusion. Patients taking anti-cytokine treatments (considered not standard) would be excluded. Other exclusions include hypercalcemia, and a history of renal failure or renal stones.
20-25 participants will be allocated to the Vitamin D Group, Arm A. 20-25 participants will be allocated to Placebo Group Arm B Allocation will be conducted in a randomized, double-blind fashion.
Summary of Procedures : After signing a written consent, all potential candidates will undergo a screening interview with the PI and screening blood tests (a blood sample of 20 ml is required).
RA subjects who qualify to receive the study treatment will be randomized to receive oral vitamin D 2,000 units or placebo daily for 6 months. Patients will be examined on a monthly basis and will be drawn a 20 ml blood sample every 2 months for monitoring purposes for a period of 12 month. The participants within the clinical trial who also participate in the translational studies on dendritic cells, will be drawn an additional blood sample of 40 ml on the first month and at the end of the study to isolate their blood dendritic cells. We will study the expression of different activation markers on dendritic cells from consenting participants using various immunologic techniques. This will allow us to identify and quantify the tolerogenic dendritic cells..
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A, | Experimental | Drug: Placebo in arm A and Vitamin D in arm BArm A: Vitamin D 2,000 units daily all in one capsule for 6 months |
| B | Placebo comparator | Drug: vitamin D 3 for arm A ,and matching placebo for arm BArm B: matching placebo one capsule daily for 6 months |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
- they should have at the time of inclusion a 25(OH)vitamin D level below 30 ng/ml.
- 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.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Placebo in arm A and Vitamin D in arm BAlso: Vitamin D3 is also called cholecalciferolVitamin 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 | Drug | A, |
| vitamin D 3 for arm A ,and matching placebo for arm BAlso: CholecalciferolArm A 2,000 units of Vitamin D3 in one capsule daily for 6 months. Arm B matching placebo capsule, one daily for 6 months | Drug | B |
Primary outcome
ACR20
Time frame: Baseline and every 2 months for 6 months
1 secondary outcome
Changes in surface marker expression of blood myeloid dendritic cells
Time frame: Baseline and at completion of study on the 6th month
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2015.
- Background: PubMed 10464556Andjelkovic 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.
- Background: PubMed 9430604Cantorna 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.
- Background: PubMed 15225816Adorini 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ernesto N Levy, MD principal investigator
India na University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study of Arthritis, Rheumatoid and Vitamin D Deficiency, run by Indiana University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 4 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ACR20 (time frame: Baseline and every 2 months for 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00279461, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Aug 2015.