Colchicine to Reduce Your SympToms And Lower Levels of Inflammation, Zeroing in on Effective CPPD Disease Treatment (CRYSTALLIZE)

A Randomized, Double-Blind, Multi-Site Placebo Controlled Trial of Colchicine in Calcium Pyrophosphate Deposition Disease

The goal of this clinical trial is to learn if colchicine reduces levels of proteins indicating inflammation in the blood in individuals with calcium pyrophosphate deposition (CPPD) disease. The trial will also test the effect of colchicine on joint symptoms in CPPD disease. The main questions it aims to answer are:

• Does colchicine reduce the level of interleukin 18 (IL-18) in the blood of individuals with CPPD disease?
• Does colchicine reduce pain scores in individuals with CPPD disease?

Researchers will compare colchicine once daily to a placebo (a look-alike pill that contains no drug) to see if colchicine works to treat CPPD disease.

Participants will:

• Take colchicine or a placebo every day for 6 months
• Visit the clinic 3 times in 6 months for joint examinations, surveys, and blood tests. Each visit will last 2-3 hours.
• Speak on the telephone with researchers for about 4 times over 6 months. Each phone call will last about 5 minutes.

Study Overview

• Status: Recruiting
• Conditions: CPPD - Calcium Pyrophosphate Deposition Disease
• Intervention / Treatment: Drug: Colchicine Pill; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sara Tedeschi, MD, MPH; Email: stedeschi1@bwh.harvard.edu
• Study Contact Backup: Name: Brenna Sharp de Flores, Senior Research Coordinator; Phone Number: 617-732-6277; Email: bsharp@bwh.harvard.edu

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Recruiting
      • University of Alabama - Birmingham
      • Contact: Shelby Gontarz, Clinical Research Coordinator; Email: sgontarz@uab.edu
      • Contact: Clementino Vong Do Rosario, Clinical Research Coordinator; Phone Number: (205) 975-6410; Email: cvongdorosario@uabmc.edu
      • Principal Investigator: Angelo Gaffo, MD, MsPH
  • California
    • Los Angeles, California, United States, 90095
      • Recruiting
      • University of California - Los Angeles
      • Contact: Michelle Ramirez, Clinical Research Coordinator; Phone Number: (310) 825-9956; Email: MichelleRa@mednet.ucla.edu
      • Contact: Aima Ohiwerei, Clinical Research Coordinator; Phone Number: (310) 825-2598; Email: AOhiwerei@mednet.ucla.edu
      • Principal Investigator: John Fitzgerald, MD, PhD
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Recruiting
      • Boston University Medical Center/Boston Medical Center
      • Contact: Sayali Dhamne, Clinical Research Coordinator; Phone Number: (617) 358-9655; Email: scdhamne@bu.edu
      • Contact: Sneha Sinha, Clinical Research Coordinator; Email: sneha@bu.edu
      • Principal Investigator: Tuhina Neogi, MD
      • Sub-Investigator: Maureen Dubreil, MD
    • Boston, Massachusetts, United States, 02118
      • Recruiting
      • Brigham and Women's Hospital
      • Contact: Brenna Sharp de Flores, Senior Research Coordinator; Phone Number: 617-732-6277; Email: bsharp@bwh.harvard.edu
      • Principal Investigator: Sara Tedeschi, MD, MPH
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Medical College of Wisconsin
      • Contact: Kiley Timler, Clinical Research Coordinator; Phone Number: (414) 955-6875; Email: ktimler@mcw.edu
      • Principal Investigator: Ann Rosenthal, MD, FACP
      • Sub-Investigator: Viktoriya Sabchyshyn, DO

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Provide written informed consent
• Fulfill ACR/EULAR 2023 CPPD classification criteria
• Acute or chronic joint inflammation currently or in the past 3 months, not attributable to another condition (Joint Inflammation defined as: At least 1 joint this is swollen, red, or warm to the touch; with or without corresponding tenderness)
• Pain visual analog scale (pain VAS) >=30 at screening

Exclusion Criteria:

• Age <40 years
• Chronic diarrhea
• Gout, rheumatoid arthritis, psoriatic arthritis, or cirrhosis
• Ongoing use of colchicine and unwilling to undergo a 30-day wash-out period (note: patients using colchicine at screening can enroll if they agree to a 30-day wash-out before randomization)
• Pregnant or breast-feeding
• Use of methotrexate, hydroxychloroquine, tocilizumab or canakinumab in the past 4 weeks
• Use of anakinra, oral glucocorticoid, or intra-articular steroid in the past 1 week
• Ongoing use of strong CYP3A4 inhibitors per FDA package insert for colchicine
• Ongoing use of P-glycoprotein inhibitors per FDA package insert for colchicine
• Known allergy to colchicine
• Planned joint surgery in the next 6 months
• CPPD clinical presentation isolated to Crowned Dens Syndrome with no additional peripheral joint involvement

• Screening labs with any of the following:

  1. Hemoglobin < 9 g/dL
  2. WBC <3 x 10^9/L
  3. Platelets <110 x10^9/L
  4. Creatinine clearance (CrCl) <30 mL/min
  5. ALT or AST >3x upper limit of normal (ULN)
• Patient is considered by investigator to be an unsuitable candidate for the study for any reason

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo capsule, taken by mouth once daily
Experimental: Colchicine	Drug: Colchicine Pill; Colchicine 0.6mg tab, overencapsulated to match placebo capsule, taken by mouth once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Interleukin 18 (IL-18)	Serum IL-18	Baseline and Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum IL-1b	Serum IL-1b	Baseline and Week 24
Serum IL-17A	Serum IL-17A	Baseline and Week 24
High-sensitivity C-reactive protein (hsCRP)	High-sensitivity C-reactive protein in blood	Baseline and Week 24
IL-1b gene signature expression in PBMCs	Expression of a panel of genes involved in IL-1b production or signaling, as percentage of total gene expression per cell	Baseline and Week 24
Immune cell population frequencies	Immune cell clusters among PBMCs	Baseline and Week 24
Patient Global Assessment of Response to Treatment	5 point Likert scale	Week 12, Week 24
Patient Global Assessment	Patient Global Assessment of CPPD Disease Activity (range: 0-10)	Baseline, Week 12, Week 24
Flare count	Number of acute calcium pyrophosphate crystal arthritis flares	Week 12, Week 24
Adverse events	Number of expected adverse events and unexpected adverse events	Week 12, Week 24
Patient Reported Outcome Measurement Information System (PROMIS)-Physical Function	PROMIS-Physical Function Short Form 10a (T-score range 0-100, with higher scores indicating better physical function)	Baseline, Week 12, Week 24
Tender Joint Count	Tender Joint Count	Baseline, Week 12, Week 24
Swollen Joint Count	Swollen Joint Count	Baseline, Week 12, Week 24
Pain visual analog scale (pain VAS)	Severity of pain from CPPD disease/pseudogout, both at rest and with activity, in the past 7 days (range 0-100mm, with 0 indicating no pain)	Baseline, Week 12, Week 24
Brief Pain Inventory (Short Form)	Brief Pain Inventory includes two sub-scores: Pain Severity Score (range 0-10, with 0 indicating no pain in the past 24 hours) and Pain Interference Score (range 0-10, with 0 indicating no interference in the past 24 hours)	Baseline, Week 12, Week 24
Pain in the past week (PEG [pain intensity [P], interference with enjoyment of life [E], and interference with general activity [G])	3 question instrument, range 0-10, with 0 indicating no pain and no interference in the past week	Baseline, Week 12, Week 24
Physician Global Assessment	Physician's Global Assessment of CPPD Disease Activity (range: 0-10)	Baseline, Week 12, Week 24

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: Rheumatology Research Foundation

Study record dates

Study Major Dates

• Study Start (Estimated): July 20, 2026
• Primary Completion (Estimated): April 30, 2030
• Study Completion (Estimated): September 30, 2030

Study Registration Dates

• First Submitted: February 26, 2025
• First Submitted That Met QC Criteria: February 26, 2025
• First Posted (Actual): March 3, 2025

Study Record Updates

• Last Update Posted (Actual): July 9, 2026
• Last Update Submitted That Met QC Criteria: July 7, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: colchicine; pseudogout; CPPD disease; calcium pyrophosphate
• Additional Relevant MeSH Terms: Crystal Arthropathies; Musculoskeletal Diseases; Arthritis; Joint Diseases; Chondrocalcinosis; Heterocyclic Compounds; Alkaloids; Colchicine
• Other Study ID Numbers: 2024P003512

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No