Does Subacromial Injection With Glutamate Receptor Antagonist, Ketamine, Attenuate Pain in Rotator Cuff Tendinopathy?

Does Subacromial Injection With Glutamate Receptor (NMDAR) Antagonist, Ketamine, Attenuate Pain in Rotator Cuff Tendinopathy?

The hypothesis of the present study is that in patients with rotator cuff tendinopathy a specific pharmacological blocking of peripheral glutamate-receptor N-methyl-d-aspartate receptor type1 (NMDAR) glutamate receptors will result in pain alleviation. Activated NMDAR1 has been demonstrated to be crucial for pain regulation in various pain disorders, and in biopsies from patients with tendinopathy, NMDAR1 was found to be activated.

To test this hypothesis a specific NMDA receptor antagonist, ketalar (ketamine), will be injected guided by ultrasound into the subacromial space in patients with rotator cuff tendinopathy, and subsequently the pain response will be assessed.

Study Overview

• Status: Recruiting
• Conditions: Chronic Pain; Rotator Cuff Tendinitis
• Intervention / Treatment: Drug: Ketalar; Drug: NaCl 9%

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Norway
  • Kristiansund, Norway
    • Recruiting
    • Department of Orthopedic Surgery, Kristiansund Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• diagnosis of rotator cuff tendinopathy by exercise-related shoulder pain with positive impingement tests as described by Hawkins and Neers, and MRI findings consistent with tendinopathy.
• Symptom duration at least 1 year to ensure neuronal ingrowth and NMDAR expression

Exclusion Criteria:

• previous surgery in any shoulder.
• previous cortisone use, either as injections or orally
• symptoms or signs of cervicobrachialgia or polyneuropathy
• full thickness rotator cuff ruptures verified by MRI
• primary inflammatory mediated pain, hence, patients with glenohumeral arthrosis, glenohumeral arthritis or systemic disorders predisposing for arthritis
• a central component of pain perception manifested by radiating pain in the involved limb; implying worse outcome after subacromial decompression.
• pregnancy
• breastfeeding
• reduced liver function (Increased serum bilirubin, ASAT or ALAT), decompensated heart failure (NYHA class 3-4)
• increased intracranial pressure or disease of the central nervous system (CNS)
• chronic alcoholism
• epilepsy
• psychiatric disease, increased intraocular pressure
• acute intermittent porphyria
• hyperthyroidism
• use of thyroid hormones
• upper respiratory tract infections
• pneumonia
• intracranial lesions
• acute head injuries
• ocular injuries
• hydrocephalus
• risk factors predisposing for intra-articular bleeding
• increased risk of infection

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketalar; ketalar injection, subacromial	Drug: Ketalar; 2,5 ml - if well tolerated immediately followed by another 2,5 ml - of an approximately 1 mg/ml ketalar solution (1 ml of ketalar 10 mg/ml + 9 ml of NaCl 9%) injected 2 times with 1-12 weeks between each injection; Other Names: Ketamine; Calypsol; Ketanest; Ketaset; Calipsol; Kalipsol; Drug: NaCl 9%; 2,5 ml - if well tolerated immediately followed by another 2,5 ml - of a 9% NaCl solution injected 2 times with 1-12 weeks between each injection
Placebo Comparator: Placebo; physiological sodium chloride (NaCl 9%) injection, subacromial	Drug: Ketalar; 2,5 ml - if well tolerated immediately followed by another 2,5 ml - of an approximately 1 mg/ml ketalar solution (1 ml of ketalar 10 mg/ml + 9 ml of NaCl 9%) injected 2 times with 1-12 weeks between each injection; Other Names: Ketamine; Calypsol; Ketanest; Ketaset; Calipsol; Kalipsol; Drug: NaCl 9%; 2,5 ml - if well tolerated immediately followed by another 2,5 ml - of a 9% NaCl solution injected 2 times with 1-12 weeks between each injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Supraspinatus pressure pain threshold	Comparison of supraspinatus pressure pain threshold measured in Lbs/cm3, after selective N-methyl-d-aspartate receptor type 1 blocking by ketalar injection subacromially controlled against ringer acetate injection	30 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Western Ontario Rotator Cuff Index	Comparisons of shoulder function assessed by Western Ontario Rotator Cuff index in the same patient group after selective N-methyl-d-aspartate receptor type 1 blocking by ketalar injection subacromially controlled against Ringer acetate injection.	30 minutes
Oxford Shoulder Score	Comparison of shoulder function assessed by Oxford Shoulder Score after selective N-methyl-d-aspartate receptor type 1 blocking by ketalar injection subacromially controlled against Ringer acetate injection.	30 minutes
Pain	Comparison of pain assessed by a visual analogue scale both at rest and abduction, after selective N-methyl-d-aspartate receptor type 1 blocking by ketalar injection subacromially controlled against Ringer acetate injection.	30 minutes
Pressure pain tolerance	Comparison of pressure pain tolerance measured in Lbs/cm3, both at rest and abduction, after selective N-methyl-d-aspartate receptor type 1 blocking by ketalar injection subacromially controlled against Ringer acetate injection.	30 minutes

Collaborators and Investigators

• Sponsor: Helse Møre og Romsdal HF

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2018
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: November 16, 2016
• First Submitted That Met QC Criteria: November 16, 2016
• First Posted (Estimate): November 18, 2016

Study Record Updates

• Last Update Posted (Actual): February 15, 2023
• Last Update Submitted That Met QC Criteria: February 14, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Shoulder; Ketamine; Analgesics; Excitatory Amino Acid Antagonists; Receptors, Glutamate
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Wounds and Injuries; Musculoskeletal Diseases; Muscular Diseases; Rupture; Shoulder Injuries; Tendon Injuries; Rotator Cuff Injuries; Chronic Pain; Tendinopathy; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Ketamine
• Other Study ID Numbers: 2012/1199; 2012-002782-35 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No