Low Dose Naltrexone Therapy for Complex Regional Pain Syndrome

NCT06306157 | Enrolling By Invitation Phase 4 DMC FDA Drug

• 1 other identifier: 2023-0667
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Complex Regional Pain Syndrome (CRPS) is a rare and often debilitating chronic pain condition whereby individuals may experience extreme sensitivity, discoloration, and swelling of the affected area -- along with numerous other painful symptoms. There are currently a limited number of treatment options available to those suffering with the condition, with various treatments including nerve blocks, neuropathic medications, and desensitization physical therapy modules. There is budding interesting in the role naltrexone, an opiate antagonist, may play in the pain management of CRPS when prescribed in very low doses. This study aims to collect preliminary data on pain scores, symptom severity, and side-effects in patients with Complex Regional Pain Syndrome randomized to receive low dose naltrexone or placebo capsules. Enrollment of 40 patients total will occur over two years from study start to study end. Each patient will be randomized to receive placebo capsules or active low dose naltrexone capsules, with both the patient and treating clinician blind to the randomization. Each patient will be actively enrolled in the study for six months and will take the medication daily at the instructed dose for the respective duration of time. Following the initial visit and study enrollment, the investigators are asking each patient to return for three (3) in-person follow-up office visits. These office visits will occur 1 month after the patient starts the medication, 3 months afterwards, and 6 months afterwards. The final 6-month office visit will mark the conclusion of the patient's active participation in the study.

Conditions

Complex Regional Pain Syndrome; Chronic Pain; Causalgia; Complex Regional Pain Syndrome Type I; Complex Regional Pain Syndrome Type II

Keywords

Chronic pain; Pain management; Drug intervention; CRPS

Outcome Measures

Primary Outcomes (3)

• Number of study patients enrolled

  Enrollment of 40 patients within two years is the target (i.e. enrollment of 1-2 patients a month). If 1-2 patients a month is not being met within first 6 months, an invitation to other chronic pain co-investigators with high volume CRPS will be considered. Because this is a feasibility study, determining whether 40 patients can be enrolled with the current inclusion and exclusion criteria within a specified time frame is an essential step in ensuring such a long-term outpatient study can be conducted.

  Within 2 years of study start

• Number of study patients randomized

  Measured as completed or not. Quadruple blinded randomization of each study patient to one of the two treatment arms after enrollment and before medication dispensation will be deemed successful. Because this is a feasibility study, determining whether 40 patients can be blindly randomized to a group according to the protocol is an essential step in ensuring such a long-term drug study can be conducted.

  At initial time of enrollment

• Number of study patients who received the study medication

  Dispensation of medication to all enrolled study patients at point of enrollment and at 3 months will be considered successful. If deemed necessary, dispensation can occur at time points other than the two previously defined and will still be considered successful if patient receives medication on time. Because this is a feasibility study implementing a long-term interventional drug treatment, it is essential that the investigators are measuring whether medication dispensation is occurring on time and according to the protocol.

  At initial time of enrollment and at 3 months.

Secondary Outcomes (6)

• Incidence of side effects/adverse events

  1, 3, and 6 months

• Average NRS pain

  Baseline, 1, 3, and 6 months.

• CRPS symptom severity

  Baseline, 1, 3, and 6 months.

• PROMIS-10 score

  Baseline, 1, 3, and 6 months

• S-LANSS score

  Baseline, 1, 3, and 6 months

Other Outcomes (5)

• Enrollment rate

  At study completion (approximately 2 years after study initiation)

• Study medication compliance

  1, 3, and 6 months

• Reasons for study medication non-compliance

  1, 3, and 6 months

Study Arms (2)

Placebo sugar capsules

PLACEBO COMPARATOR

Half of all enrolled patients will be randomized to receive placebo sugar capsules. Neither the patient nor treating physician will be aware of the group in which the patient was randomized into until after study conclusion. All patients will be requested to take the respective daily dose and follow the titration schedule as instructed. All patients enrolled in the study, regardless of their randomization, will have standard of care treatment for CRPS according to their symptoms and the clinical judgment of the treating clinician.

Drug: Placebo sugar capsules

Low dose naltrexone

EXPERIMENTAL

Half of all enrolled patients will be randomized to receive capsules with the active low dose naltrexone (LDN) ingredient. LDN will be titrated over time to minimize potential side effects, with the initial dose starting at 1.5mg and eventually increasing up to 4.5mg. Neither the patient nor treating physician will be aware of the group in which the patient was randomized into until after study conclusion. All patients will be requested to take the respective daily dose and follow the titration schedule as instructed. All patients enrolled in the study, regardless of their randomization, will have standard of care treatment for CRPS according to their symptoms and the clinical judgment of the treating clinician.

Drug: Low dose naltrexone

Interventions

Low dose naltrexone DRUG

While naltrexone is FDA-approved for treatment of alcohol or opioid addition, this study will be looking at how naltrexone, when dosed very low, may reduce the painful symptoms associated with CRPS. Naltrexone is not FDA-approved for pain management treatment of CRPS at this time, and therefore the study intervention is using the drug in an off-label manner.

Also known as: LDN

Low dose naltrexone

Placebo sugar capsules DRUG

The external appearance of the capsules prepared by the pharmacy will be identical to the LDN capsules. The inactive capsule ingredients will be microcrystalline cellulose (MCC) and Magnesium stearate

Placebo sugar capsules

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Between 18 and 65 years old
• Meeting CRPS diagnostic criteria using the Budapest Clinical Diagnostic Criteria
• CRPS patients with severe pain (NRS\>3) that affects their daily life.
• CRPS patients with pain and other symptoms for more than 3 months.

You may not qualify if:

• Patients with suspected disc herniation, spinal stenosis, myelopathy, and suspected radiculopathy in detailed examinations and examinations (MRI, CT).
• Systemic or local infection
• Malignancy
• Current or planned pregnancy within the study period.
• Uncontrolled medical and psychiatric condition
• Patients with known liver issues, including but not limited to end-stage liver disease, severe cirrhosis or an acute hepatic state.
• Patients who are currently using opioid drugs
• Patients who are currently using alcohol or considering using alcohol during the study period.
• Allergy to naltrexone or naloxone

Sponsors & Collaborators

• Hospital for Special Surgery, New York: lead

Study Sites (1)

Hospital for Special Surgery

New York, New York, 10021, United States

Location

Related Publications (2)

• Toljan K, Vrooman B. Low-Dose Naltrexone (LDN)-Review of Therapeutic Utilization. Med Sci (Basel). 2018 Sep 21;6(4):82. doi: 10.3390/medsci6040082.

  PMID: 30248938 BACKGROUND

• Chopra P, Cooper MS. Treatment of Complex Regional Pain Syndrome (CRPS) using low dose naltrexone (LDN). J Neuroimmune Pharmacol. 2013 Jun;8(3):470-6. doi: 10.1007/s11481-013-9451-y. Epub 2013 Apr 2.

  PMID: 23546884 BACKGROUND

MeSH Terms

Conditions

Complex Regional Pain Syndromes; Chronic Pain; Causalgia; Agnosia

Interventions

Naltrexone

Condition Hierarchy (Ancestors)

Autonomic Nervous System Diseases; Nervous System Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neuralgia; Perceptual Disorders; Neurobehavioral Manifestations

Intervention Hierarchy (Ancestors)

Naloxone; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Semih Gungor, M.D.

  Hospital for Special Surgery, New York

  PRINCIPAL INVESTIGATOR

• Alexandra Sideris, PhD

  Hospital for Special Surgery, New York

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: A quadruple blinded study where the patient, research team, treating clinician, and outcomes assessor are unaware of the randomization results until after study conclusion. The research pharmacy will not be blinded and will be responsible for preparing the medication and securely handing it off to the research assistant according to the pre-approved dispensation plan.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a feasibility, randomized, placebo-controlled interventional drug study.

Study Record Dates

• First Submitted: February 27, 2024
• First Posted: March 12, 2024
• Study Start: January 2, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: November 26, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 9 months and ending 36 months following article publication
• Access Criteria: For researchers who provide a methodologically sound proposal and analyses to achieve aims in the approved proposal. Proposals should be directed to siderisa@hss.edu. To gain access, data requestors will need to sign a data access agreement.

Locations

US (1)