Effects of Allopurinol on Inflammation and Ultrasonographic Changes in People With Elevated Uric Acid But no Symptoms

NCT04012294 | Unknown Phase 3

• 1 other identifier: CardiologiaIC
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 2

Brief Summary

Hyperuricemia is a metabolic alteration defined as the presence of serum urate levels higher than 7 mg/dL. This has proven to be the maximum limit of solubility of urate in serum, any higher concentration leads to precipitation and eventually to the formation of monosodium urate (MSU) crystals. The accumulation of said crystals can manifest as gouty arthritis, uric acid nephropathy, urolithiasis or chronic tophaceous gout. A strong relation between hyperuricemia and other chronic degenerative diseases, including diabetes mellitus, systemic arterial hypertension, obesity and metabolic syndrome, has been consistently proven. Hypouricemic pharmacological agents have shown a decrease in cardiovascular complications and death in patients with gout. A series of studies conducted on individuals with asymptomatic hyperuricemia using musculoskeletal ultrasound (MSUS) have shown the presence of morphostructural changes suggestive of MSU crystal deposits, combined with an elevation in a series of inflammation markers to a degree similar to those found in patients with chronic gout. Even though, there is evidence of morphostructural damage in individuals with asymptomatic hyperuricemia, there are no clinical, laboratorial or imaging parameters that indicate when hypouricemic treatment should be started. This clinical trial is proposed as a proof of concept which is looking to evaluate if treatment with allopurinol induces changes in levels of inflammatory markers in individuals with asymptomatic hyperuricemia and morphostructural changes suggestive of MSU crystal deposits. this proof of concept is not looking to measure the efficiency, effectiveness or security of the treatment. Our Hypothesis is that Individuals with asymptomatic hyperuricemia and morphostructural changes evidenced by MSUS (double contour sing, tophi, aggregates) will show a decent in inflammatory markers and their morphostructural changes will diminish or revert after treatment with allopurinol.

Conditions

Musculoskeletal Degeneration; Inflammation; Hyperuricemia

Keywords

allopurinol; ultrasound; morphostructural changes

Outcome Measures

Primary Outcomes (10)

• inflammatory markers

  To measure changes in proinflammatory cytokines (Interleukin 1ß (IL-1ß))

  6 months

• inflammatory markers

  To measure changes in proinflammatory cytokines (Tumor Necrosis Factor)

  6 months

• inflammatory markers

  To measure changes in proinflammatory cytokines (Interleukin 6 (IL-6))

  6 months

• inflammatory markers

  To measure changes in proinflammatory cytokines (Interferon-γ)

  6 months

• inflammatory markers

  To measure changes in proinflammatory cytokines (Interleukin 18 (IL-18))

  6 months

• inflammatory markers

  To measure changes in proinflammatory cytokines (Interleukin 17 (IL-17))

  6 months

• inflammatory markers

  To measure changes in chemokines (Interleukin 8 (IL-8))

  6 months

• inflammatory markers

  To measure changes in chemokines (monocyte chemoattractant protein 1 (MCP-1))

  6 months

• inflammatory markers

  To measure changes in microRNAs (miR) (miR-155)

  6 months

• inflammatory markers

  To measure changes in the percentage of Cluster of Differentiation 4 cells that lack the expression of Cluster of Differentiation 28 (CD4+CD28null)

  6 months

Secondary Outcomes (4)

• musculoskeletal ultrasound

  6 months

• musculoskeletal ultrasound

  6 months

• musculoskeletal ultrasound

  6 months

• musculoskeletal ultrasound

  6 months

Study Arms (1)

allopurinol

EXPERIMENTAL

150 mg daily for a month then 300 mg daily for the rest of the study (5 months)

Drug: Allopurinol Pill

Interventions

Allopurinol Pill DRUG

Individuals who meet the inclusion criteria and also have morphostructural changes suggestive of MSU crystal deposits in their MSUS will start treatment with allopurinol at a dosage of 150 mg to be taken daily, orally for a month and then to be increased to 300 mg. The rest of the individuals' medication is not to be altered. If a participant presents hypersensitivity to allopurinol, they are to stop the medication and will be excluded from the investigation. Three months after starting treatment, the participants will have a physical exam, confirm the continuation of the treatment (adjust dosage if needed) and take a blood sample for laboratory tests. Six months after treatment is started, the participants will be reevaluated by MSUS and have another blood sample taken, Once the study is finished, continuing or ending treatment with allopurinol will be decided by the medical judgment of the physician of each participant.

Also known as: Zyloprim

allopurinol

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Individuals with two urate determinations \>7 mg/dL in the last year and no clinical sign, past or present, suggestive of joint inflammation (acute gout attack), urolithiasis or uric acid nephropathy
• Over 18 years of age
• Residents of Mexico City or its metropolitan area
• Individuals with a signed informed consent form for the participation in the clinical trial

You may not qualify if:

• Individuals with joint inflammation suggestive of gout during the clinical evaluation
• Patients without elemental ultrasonographic lesions (double contour sign, aggregates, tophi) on the first metatarsophalangeal joint, knee, ankle or the tendons of the quadriceps, patella, and calcaneus when evaluated by MSUS
• Patients taking thiazides
• Patients with history of stroke or coronary artery disease in the last year
• Patients with osteoarthritis be it by clinical presentation or imaging
• Pregnant women
• Neoplasms
• Known Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) , Human immunodeficiency Virus (HIV) infection, or any other know active infections
• Autoimmune or autoinflammatory disease
• Allopurinol hypersensitivity or allergy
• Deteriorated kidney function (Glomerular Filtration Rate (GFR) \<50 mL/min/1.73m\^2)
• Patients taking azathioprine
• Functional New York Heart Association (NYHA) score of II or more

Sponsors & Collaborators

• Instituto Nacional de Cardiologia Ignacio Chavez: lead
• Instituto Nacional de Rehabilitacion: collaborator

Study Sites (2)

Instituto Nacional de Cardiología

Mexico City, 14080, Mexico

RECRUITING

National Institute of Cardiology Mexico

Mexico City, 14080, Mexico

RECRUITING

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MeSH Terms

Conditions

Inflammation; Hyperuricemia

Interventions

Allopurinol

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Luis M Amezcua-Guerra, MD

  Instituto Nacional de Cardiologia Ignacio Chavez

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Luis M Amezcua-Guerra, MD

CONTACT

55732911; lmamezcuag@gmail.com

Carlos Pineda, MD

CONTACT

59991000; carpineda@yahoo.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Immunology Department, Principal Investigator

Study Record Dates

• First Submitted: July 3, 2019
• First Posted: July 9, 2019
• Study Start: August 30, 2019
• Primary Completion: July 30, 2020
• Study Completion: February 28, 2021
• Last Updated: January 23, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

ME (2)