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

Sponsor

Helse Møre og Romsdal HF (Other)

Overall Status

Recruiting

CT.gov ID

NCT02967640

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Rotator Cuff Tendinitis Chronic Pain	Drug: Ketalar Drug: NaCl 9%	Phase 2/Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double (Participant, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

May 1, 2018

Anticipated Primary Completion Date :

May 1, 2022

Anticipated Study Completion Date :

May 1, 2022

Arms and Interventions

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 Ketanest Ketaset Calipsol Kalipsol Calypsol 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 Ketanest Ketaset Calipsol Kalipsol Calypsol 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

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

Ketanest

Ketaset

Calipsol

Kalipsol

Calypsol

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

Other Names:

Ketamine

Ketanest

Ketaset

Calipsol

Kalipsol

Calypsol

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

Outcome Measures

Primary Outcome Measures

Supraspinatus pressure pain threshold [30 minutes]
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

Secondary Outcome Measures

Western Ontario Rotator Cuff Index [30 minutes]
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.
Oxford Shoulder Score [30 minutes]
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.
Pain [30 minutes]
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.
Pressure pain tolerance [30 minutes]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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