The Use of Zoledronic Acid to Complex Regional Pain Syndrome (Aclasta)

Phase 2 Study - The Use of a Single 5 mg Dose of Zoledronic Acid in Complex Regional Pain Syndrome Patient.

To evaluate the efficacy and the safety of using a single, intravenous 5mg dose of zoledronic acid in managing pain in Complex Regional Pain Syndrome patients.

Study Overview

• Status: Unknown
• Conditions: Complex Regional Pain Syndromes
• Intervention / Treatment: Drug: Placebo; Drug: Zoledronic acid

Detailed Description

Complex regional pain syndrome (CRPS) is a disorder of the extremities that is characterized by spontaneous unexplained disproportionate pain, hyperalgesia, swelling, limited range of motion, vasomotor instability, skin changes, and patchy bone demineralization.The incidence of CRPS was estimated to be 5.46 per 100,000 person years at risk in Olmsted County, Minnesota (US), with a prevalence of 20.57 per 100,000, while its incidence in the general population of the Netherlands was estimated to be much higher, at 26.2 per 100,000 person-years. The adverse effects were not serious and lasted just a few days. The beneficial effects of other bisphosphonates have been already documented in several placebo-controlled trials; however, there are no reports on the use of zoledronic acid to reduce pain in CRPS patients.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Perola Grinberg Plapler, MD; Phone Number: 55 11 39058512; Email: perolagp@yahoo.com
• Study Contact Backup: Name: Marta Imamura, MD; Phone Number: 55 11 39058512; Email: martimf3@gmail.com

Study Locations

• Brazil
  • São Paulo, Brazil, 05716-150
    • Centro de Pesquisa Clínica do Instituto de Medicina e Reabilitação do HCFMUSP
    • Contact: Pérola G Plapler, MDPhD; Phone Number: 55 11 39058512; Email: perolagp@yahoo.com
    • Contact: Marta Imamura, MDPhD; Phone Number: 55 11 39058512; Email: martaimf3@gmail.com
    • Principal Investigator: Pérola G. Plapler, MDPhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients over 18 years of age of both genders, with continuing pain that is disproportionate to any inciting event, with cardinal features of CRPS.
2. Pain - after initial injury with signs and symptoms present at first visit
3. History of previous unsuccessful treatment for pain, with a minimum of two drug therapies, such as non steroidal anti-inflammatory drugs, steroids, antidepressants, central acting analgesics, calcitonin or sympathetic blocks, (not bisphosphonates) for at least six months.

4. Must report at least one symptom in three of the four following categories:

   1. Sensory: Reports of hyperesthesia and/or allodynia
   2. Vasomotor: Reports of temperature asymmetry and/or skin color changes and/or skin color asymmetry
   3. Sudomotor/Edema: Reports of edema and/or sweating changes and/or sweating asymmetry
   4. Motor/Trophic: Reports of decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nail, skin).

5. Must display at least one sign* at time of evaluation in two or more of the following categories:

   1. Sensory: Evidence of hyperalgesia (to pinprick) and/or allodynia (to light touch and/or deep somatic pressure and/or joint movement)
   2. Vasomotor: Evidence of temperature asymmetry and/or skin color changes and/or asymmetry
   3. Sudomotor/Edema: Evidence of edema and/or sweating changes and/or sweating asymmetry
   4. Motor/Trophic: Evidence of decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nail, skin).
6. Skin temperature of the affected side equal or higher than on the non-affected side.
7. No other diagnosis better explains the signs and symptoms.

Exclusion Criteria:

1. Presence of systemic diseases including diabetes mellitus, hyperthyroidism, renal and liver dysfunction, peripheral vascular or cardiovascular diseases, uncontrolled hypertension, rheumatoid and hematopoietic diseases, neurological diseases not related to CRPS, overt alcohol addiction, positive pregnancy test and/or lactating women, hyperparathyroidism, and hypocalcaemia.
2. Creatinine clearance <35mL/min, with serum creatinine measured before the dose of zoledronic acid.
3. Pre-existing hypocalcaemia and disturbance of mineral metabolism (e.g. hyperparathyroidism, thyroid surgery, parathyroid surgery, malabsorption syndromes, and excision of small intestine).
4. Hypersensitivity to zoledronic acid or any component drugs used in the trial.
5. Patients with asthma and aspirin-sensitivity
6. Pregnancy or unwillingness to use contraceptive methods during the trial
7. Patients who have previously used any kind of bisphosphonate, especially zoledronic acid.
8. Osteoporosis

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Saline; One single intravenous infusion of 100ml of saline (placebo control group).	Drug: Placebo; one single intravenous infusion of 100ml of saline.
Active Comparator: Zoledronic acid; one single dose of 5mg intravenous infusion of zoledronic acid (interventional group)	Drug: Zoledronic acid; One single dose of 5mg intravenous infusion of zoledronic acid (interventional group)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pain measured on Visual Analog Scale	up to 12 months after treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Lower Limbs vertical force on Wii platform	Baseline, 3, 6 and 12 months
American Orthopaedic Foot and Ankle Scale (AOFAS)	Baseline, 3, 6 and 12 months after treatment
36-Item Short Form Health Survey (SF-36)	Baseline, 3, 6 and 12 months after treatment

Collaborators and Investigators

• Sponsor: University of Sao Paulo General Hospital
• Collaborators: Novartis
• Investigators: Study Director: Linamara R. Battistella, PHD, Centro de Pesquisa Clínica do Instituto de Medicina Física e de Reabilitação do Hospital das Clínicas da FMUSP

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Anticipated): December 1, 2015
• Study Completion (Anticipated): December 1, 2016

Study Registration Dates

• First Submitted: October 9, 2012
• First Submitted That Met QC Criteria: February 8, 2013
• First Posted (Estimate): February 11, 2013

Study Record Updates

• Last Update Posted (Estimate): February 11, 2013
• Last Update Submitted That Met QC Criteria: February 8, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Keywords: drug therapy; zoledronic acid; Complex Regional Pain Syndromes
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Disease; Neuromuscular Diseases; Peripheral Nervous System Diseases; Autonomic Nervous System Diseases; Syndrome; Complex Regional Pain Syndromes; Reflex Sympathetic Dystrophy; Somatoform Disorders; Physiological Effects of Drugs; Bone Density Conservation Agents; Zoledronic Acid
• Other Study ID Numbers: CZOL446HBR10T