Nicotinamide Treatment for Lupus-associated Skin Lesions in Lupus Erythematosus

Cutaneous Lupus Erythematosus Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03260166
• Other study ID #: PFK201707
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 31, 2017
• Est. completion date: July 1, 2021

Study information

• Verified date: January 2021
• Source: Second Xiangya Hospital of Central South University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: July 1, 2021
• Est. primary completion date: January 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Age: between 18 years and 65 years.

2. 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.

3. 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.

4. 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.

5. Written informed consent form.

Exclusion Criteria:

1. 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.

2. 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).

3. A history of treatment with nicotinamide, niacin, or multi-vitamins in the recent month.

4. 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.

5. 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.

6. Patients with drug abuse, alcohol abuse, or mental disorders that are unable to cooperate or adhere to treatment.

7. Pregnancy or lac¬tation in females.

8. Participants in other clinical trials.

Related Conditions & MeSH terms

• Cutaneous Lupus Erythematosus
• Lupus Erythematosus, Cutaneous
• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus Rash

Intervention

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

Locations

Country	Name	City	State
China	The Second Xiangya Hospital of Central South University	Changsha	Hunan

Sponsors (4)

Lead Sponsor	Collaborator
Second Xiangya Hospital of Central South University	Hunan Provincial Natural Science Foundation of China, National Key Clinical Specialty Construction Project of China, National Natural Science Foundation of China

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	from baseline (at visit 0) to 3 months treatment (at visit 3)
Secondary	A change in RCLASI activity score	The higher the RCLASI score, the worse of the lupus-associated skin lesion is.	from baseline (at visit 0) to 1, 2, 4, and 6 months treatment (at visit 1, 2, 4, and 5), respectively
Secondary	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.	1 month, 2 months, 3 months, 4 months, and 6 months
Secondary	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.	4 months, 6 months
Secondary	A change in Dermatology Life Quality Index (DLQI) score	DLQI reflect the quality of life related to skin manifestations.	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
Secondary	A change in Physician's Global Assessment (PGA) score		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
Secondary	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.	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
Secondary	A change in the serum level of cytokines interferon (IFN)?, interleukin (IL)-4, IL-17A, transforming growth factor (TGF)-ß, IL-10, IL-21, and IL-6	At each time point, the serum level of cytokines IFN?, IL-4, IL-17A, TGF-ß, 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.	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
Secondary	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	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
Secondary	A change in the results of urine sediment test	This is for evaluation of the potential effects of nicotinamide on renal damage.	1 month, 2 months, 3 months, 4 months, and 6 months
Secondary	Dose reduction of concomitant corticosteroids		from baseline (at visit 0) to 3 months, 4 months, and 6 months (at visit 3, 4, and 5), respectively
Secondary	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.	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
Secondary	A change in British Isles Lupus Assessment Group 2004 Index (BILAG-2004)	This outcome is only evaluated for patients with SLE.	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
Secondary	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.	3 months
Secondary	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.	6 months