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Nicotinamide Treatment for Lupus-associated Skin Lesions in Lupus Erythematosus

Primary Purpose

Cutaneous Lupus Erythematosus, Systemic Lupus Erythematosus Rash

Status

Unknown status

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

nicotinamide

About this trial

This is an interventional treatment trial for Cutaneous Lupus Erythematosus focused on measuring nicotinamide, lupus-associated skin lesion, lupus erythematosus

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age: between 18 years and 65 years.
Patients clinically and histopathologically diagnosed as cutaneous lupus erythematosus (CLE) that have not respond to treatment with hydroxychloroquine (200-400 mg/day) plus corticosteroids at a dosage less than the equivalent of 0.5mg/kg/day of prednisone for the preceding two months or a longer period.
Patients diagnosed as SLE (meeting the 1997 American College of Rheumatology criteria for SLE) that present with lupus-associated skin lesions that have not respond to treatment with hydroxychloroquine (200-400 mg/day) plus corticosteroids at a dosage less than the equivalent of 0.5mg/kg/day of prednisone for the preceding two months or a longer period.
Revised Cutaneous Lupus Erythematosus Disease Area and Severity Index (RCLASI) ≥4; for patients with SLE, Safety of Estrogens in Lupus Erythematosus National Assessment version of the systemic lupus erythematosus disease activity index (SELENA-SLEDAI) is within the range between 0 and 9.
Written informed consent form.

Exclusion Criteria:

Severe comorbidities including heart failure (≥grade III NYHA), respiratory failure, renal insufficiency (creatinine clearance ≤30 ml/min), hepatic insuf¬ficiency (alanine aminotransferase or aspartate aminotransferase ≥2 times of the upper limit of the normal range), or active severe neuropsychiatric manifestations of SLE.
Acute severe infection such as sepsis and cellulitis, or a history of infection of hepatitis B or C virus, Mycobacterium tuberculosis, or human immunodeficiency virus (HIV).
A history of treatment with nicotinamide, niacin, or multi-vitamins in the recent month.
A history of treatment with rituximab or other biologics; or a history of treatment with high-dose corticosteroids (≥1.5 mg/kg/d), immunosuppressants, tripterygium glycosides, or intravenous immunoglobin G (IVIG) in the preceding three months.
Patients not suitable for using nicotinamide due to comorbidities including pruritic skin diseases such as atopic dermatitis and urticaria, vertigo, dizziness, headache, hyperglycemia, and hyperuricemia; patients not suitable for using hydroxychloroquine due to conditions including retinopathy or hypersensitivity to hydroxychloroquine.
Patients with drug abuse, alcohol abuse, or mental disorders that are unable to cooperate or adhere to treatment.
Pregnancy or lac¬tation in females.
Participants in other clinical trials.

Sites / Locations

The Second Xiangya Hospital of Central South University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

nicotinamide

Arm Description

Patients will receive 10 nicotinamide tablets orally twice daily (nicotinamide 500 mg, p.o., Bid) for a period of 3 months. Each tablet contains 50 mg of nicotinamide.

Outcomes

Primary Outcome Measures

A change in Revised Cutaneous Lupus Erythematosus Disease Area and Severity Index (RCLASI) activity score

The higher the RCLASI score, the worse of the lupus-associated skin lesion is.

Secondary Outcome Measures

A change in RCLASI activity score

The higher the RCLASI score, the worse of the lupus-associated skin lesion is.

Response Rate and Remarkable Response Rate at 1, 2, 3, 4, and 6 months, respectively

Response is defined as a ≥ 4-point reduction or a ≥20% reduction in RCALSI activity score. Remarkable Response is defined as a ≥50% reduction in RCALSI activity score.

Number of Relapses

Relapse means that if the patient's RCLASI activity score has a ≥ 4-point reduction or a ≥20% reduction than at baseline during the 3-month treatment, and then the RCLASI activity score increase to be no lower than at baseline after stopping using nicotinamide in the following 3 months.

A change in Dermatology Life Quality Index (DLQI) score

DLQI reflect the quality of life related to skin manifestations.

A change in Physician's Global Assessment (PGA) score

A change in the percentage of different T helper cell (Th) subsets among CD4+ T lymphocytes

At each time point, the percentage of Th1, Th2, Th17, regulatory T cell (Treg), and follicular helper T cell (Tfh) subsets among CD4+ T lymphocytes in peripheral venous blood of the patient will be measured by flow cytometry. 5 ml of peripheral venous blood will be collected from the patient at each time point, of which 4.5 ml will be used in this flow cytometry assay.

A change in the serum level of cytokines interferon (IFN)γ, interleukin (IL)-4, IL-17A, transforming growth factor (TGF)-β, IL-10, IL-21, and IL-6

At each time point, the serum level of cytokines IFNγ, IL-4, IL-17A, TGF-β, IL-10, IL-21, and IL-6 in the patient's venous blood will be measured using enzyme linked immunosorbent assay (ELISA) or Bio-Plex methods. 5 ml of peripheral venous blood will be collected from the patient at each time point, of which 0.5 ml will be used in this ELISA or Bio-Plex assay.

A change in serum levels of complement 3 (C3), C4, and C1q

This is for evaluation of the potential effects of nicotinamide on serum levels of complements that are associated with lupus activity

A change in the results of urine sediment test

This is for evaluation of the potential effects of nicotinamide on renal damage.

Dose reduction of concomitant corticosteroids

A change in SELENA-SLEDAI (Safety of Estrogens in Lupus Erythematosus National Assessment version of the systemic lupus erythematosus disease activity index)

This outcome is only evaluated for patients with SLE.

A change in British Isles Lupus Assessment Group 2004 Index (BILAG-2004)

This outcome is only evaluated for patients with SLE.

Incidence of side effects

Possible side effects of nicotinamide include flushing and itching of the skin, cardiac arrhythmia, dizziness, nausea, epigastric discomfort, loss of appetite, elevated blood glucose, and elevated blood uric acid. The major side effects of HCQ that need to be monitored include retina toxicity.

Incidence of side effects

Full Information

NCT ID

NCT03260166

First Posted

August 10, 2017

Last Updated

January 31, 2021

Sponsor

Second Xiangya Hospital of Central South University

Collaborators

National Natural Science Foundation of China, Hunan Provincial Natural Science Foundation of China, National Key Clinical Specialty Construction Project of China

1. Study Identification

Unique Protocol Identification Number

NCT03260166

Brief Title

Nicotinamide Treatment for Lupus-associated Skin Lesions in Lupus Erythematosus

Official Title

An Open-label Study for Assessing the Efficacy and Safety of Nicotinamide Treatment for Lupus-associated Skin Lesions in Patients With Cutaneous Lupus Erythematosus or Systemic Lupus Erythematosus

Study Type

Interventional

2. Study Status

Record Verification Date

January 2021

Overall Recruitment Status

Unknown status

Study Start Date

August 31, 2017 (Actual)

Primary Completion Date

January 1, 2020 (Actual)

Study Completion Date

July 1, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Second Xiangya Hospital of Central South University

Collaborators

National Natural Science Foundation of China, Hunan Provincial Natural Science Foundation of China, National Key Clinical Specialty Construction Project of China

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

5. Study Description

Brief Summary

This clinical study will test the efficacy and safety of nicotinamide for lupus-associated skin lesions refractory to the treatment of hydroxychloroquine plus low-dose corticosteroids in patients with cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE).

Detailed Description

Backgrounds: Lupus erythematosus (LE) is an autoimmune disease affecting various organs. Lupus-associated skin lesions are the dominant clinical manifestations of cutaneous lupus erythematosus (CLE) and also occur in 70%~80% of patients with systemic lupus erythematosus (SLE), and usually involve the sunlight-exposure sites such as the face, neck and hands, which affects the personal appearance dramatically and causes substantial psychological impact to the patients. While antimalarials such as hydroxychloroquine (HCQ) have been widely used as a first-line treatment for lupus-associated skin lesions, 30% of patients with lupus do not respond to this medication. Other available therapies such as corticosteroids and thalidomide can also be applied, however, their toxic side effects limit the clinical use. Recent studies by the investigators have shown that nicotinamide, a water-soluble vitamin whose side effects are considered as minimal, can protect MRL/lpr mice (a lupus-like mouse model) from skin lesions and autoantibody production. Thus it is hypothesized that nicotinamide treatment could be a novel therapy for lupus-associated skin lesions in patients with LE. Design of Study: This is a single center, uncontrolled, open-label study to assess the efficacy and safety of nicotinamide for lupus-associated skin lesions refractory to the treatment of HCQ plus low-dose corticosteroids in patients with CLE or SLE. Methods: For CLE or SLE patients with lupus-associated skin lesions scoring >=4 on the Revised Cutaneous Lupus Erythematosus Disease Area and Severity Index (RCLASI) that have been refractory to the treatment of HCQ plus low-dose corticosteroids (<=0.5 mg/kg/d) during the past two months, oral nicotinamide (500 mg twice daily) will be given consecutively for 3 months while the current regimen including HCQ and corticosteroids be maintained without change. The end points include clinical response and immunological changes, as well as safety.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cutaneous Lupus Erythematosus, Systemic Lupus Erythematosus Rash

Keywords

nicotinamide, lupus-associated skin lesion, lupus erythematosus

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

nicotinamide

Arm Type

Experimental

Arm Description

Patients will receive 10 nicotinamide tablets orally twice daily (nicotinamide 500 mg, p.o., Bid) for a period of 3 months. Each tablet contains 50 mg of nicotinamide.

Intervention Type

Drug

Intervention Name(s)

nicotinamide

Other Intervention Name(s)

Niacinamide

Intervention Description

Drug: nicotinamide; Pharmaceutical form: tablet; Route of administration: oral

Primary Outcome Measure Information:

Title

A change in Revised Cutaneous Lupus Erythematosus Disease Area and Severity Index (RCLASI) activity score

Description

The higher the RCLASI score, the worse of the lupus-associated skin lesion is.

Time Frame

from baseline (at visit 0) to 3 months treatment (at visit 3)

Secondary Outcome Measure Information:

Title

A change in RCLASI activity score

Description

The higher the RCLASI score, the worse of the lupus-associated skin lesion is.

Time Frame

from baseline (at visit 0) to 1, 2, 4, and 6 months treatment (at visit 1, 2, 4, and 5), respectively

Title

Response Rate and Remarkable Response Rate at 1, 2, 3, 4, and 6 months, respectively

Description

Response is defined as a ≥ 4-point reduction or a ≥20% reduction in RCALSI activity score. Remarkable Response is defined as a ≥50% reduction in RCALSI activity score.

Time Frame

1 month, 2 months, 3 months, 4 months, and 6 months

Title

Number of Relapses

Description

Time Frame

4 months, 6 months

Title

A change in Dermatology Life Quality Index (DLQI) score

Description

DLQI reflect the quality of life related to skin manifestations.

Time Frame

from baseline (at visit 0) to 1 month, 2 months, 3 months, 4 months, and 6 months (at visit 1, 2, 3, 4, and 5), respectively

Title

A change in Physician's Global Assessment (PGA) score

Time Frame

from baseline (at visit 0) to 1 month, 2 months, 3 months, 4 months, and 6 months (at visit 1, 2, 3, 4, and 5), respectively

Title

A change in the percentage of different T helper cell (Th) subsets among CD4+ T lymphocytes

Description

Time Frame

from baseline (at visit 0) to 1 month, 2 months, 3 months, 4 months, and 6 months (at visit 1, 2, 3, 4, and 5), respectively

Title

A change in the serum level of cytokines interferon (IFN)γ, interleukin (IL)-4, IL-17A, transforming growth factor (TGF)-β, IL-10, IL-21, and IL-6

Description

Time Frame

from baseline (at visit 0) to 1 month, 2 months, 3 months, 4 months, and 6 months (at visit 1, 2, 3, 4, and 5), respectively

Title

A change in serum levels of complement 3 (C3), C4, and C1q

Description

This is for evaluation of the potential effects of nicotinamide on serum levels of complements that are associated with lupus activity

Time Frame

from baseline (at visit 0) to 1 month, 2 months, 3 months, 4 months, and 6 months (at visit 1, 2, 3, 4, and 5), respectively

Title

A change in the results of urine sediment test

Description

This is for evaluation of the potential effects of nicotinamide on renal damage.

Time Frame

1 month, 2 months, 3 months, 4 months, and 6 months

Title

Dose reduction of concomitant corticosteroids

Time Frame

from baseline (at visit 0) to 3 months, 4 months, and 6 months (at visit 3, 4, and 5), respectively

Title

A change in SELENA-SLEDAI (Safety of Estrogens in Lupus Erythematosus National Assessment version of the systemic lupus erythematosus disease activity index)

Description

This outcome is only evaluated for patients with SLE.

Time Frame

from baseline (at visit 0) to 1 month, 2 months, 3 months, 4 months, and 6 months (at visit 1, 2, 3, 4, and 5), respectively

Title

A change in British Isles Lupus Assessment Group 2004 Index (BILAG-2004)

Description

This outcome is only evaluated for patients with SLE.

Time Frame

from baseline (at visit 0) to 1 month, 2 months, 3 months, 4 months, and 6 months (at visit 1, 2, 3, 4, and 5), respectively

Title

Incidence of side effects

Description

Time Frame

3 months

Title

Incidence of side effects

Description

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age: between 18 years and 65 years. Patients clinically and histopathologically diagnosed as cutaneous lupus erythematosus (CLE) that have not respond to treatment with hydroxychloroquine (200-400 mg/day) plus corticosteroids at a dosage less than the equivalent of 0.5mg/kg/day of prednisone for the preceding two months or a longer period. Patients diagnosed as SLE (meeting the 1997 American College of Rheumatology criteria for SLE) that present with lupus-associated skin lesions that have not respond to treatment with hydroxychloroquine (200-400 mg/day) plus corticosteroids at a dosage less than the equivalent of 0.5mg/kg/day of prednisone for the preceding two months or a longer period. Revised Cutaneous Lupus Erythematosus Disease Area and Severity Index (RCLASI) ≥4; for patients with SLE, Safety of Estrogens in Lupus Erythematosus National Assessment version of the systemic lupus erythematosus disease activity index (SELENA-SLEDAI) is within the range between 0 and 9. Written informed consent form. Exclusion Criteria: Severe comorbidities including heart failure (≥grade III NYHA), respiratory failure, renal insufficiency (creatinine clearance ≤30 ml/min), hepatic insuf¬ficiency (alanine aminotransferase or aspartate aminotransferase ≥2 times of the upper limit of the normal range), or active severe neuropsychiatric manifestations of SLE. Acute severe infection such as sepsis and cellulitis, or a history of infection of hepatitis B or C virus, Mycobacterium tuberculosis, or human immunodeficiency virus (HIV). A history of treatment with nicotinamide, niacin, or multi-vitamins in the recent month. A history of treatment with rituximab or other biologics; or a history of treatment with high-dose corticosteroids (≥1.5 mg/kg/d), immunosuppressants, tripterygium glycosides, or intravenous immunoglobin G (IVIG) in the preceding three months. Patients not suitable for using nicotinamide due to comorbidities including pruritic skin diseases such as atopic dermatitis and urticaria, vertigo, dizziness, headache, hyperglycemia, and hyperuricemia; patients not suitable for using hydroxychloroquine due to conditions including retinopathy or hypersensitivity to hydroxychloroquine. Patients with drug abuse, alcohol abuse, or mental disorders that are unable to cooperate or adhere to treatment. Pregnancy or lac¬tation in females. Participants in other clinical trials.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Qianjin Lu, MD, PhD

Organizational Affiliation

Central South University

Official's Role

Principal Investigator

Facility Information:

Facility Name

The Second Xiangya Hospital of Central South University

City

Changsha

State/Province

Hunan

ZIP/Postal Code

410011

Country

China

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Nicotinamide Treatment for Lupus-associated Skin Lesions in Lupus Erythematosus

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