Opioid Induced Gait Variability

Study Overview
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Brief Summary
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While the analgesic effects of opioids are well known, evidence suggest that there are differences in the adverse dizziness of the different opioid types, which may influence the gait function differently. However, this has not been investigated scientifically under controlled conditions. Normal gait function is characterized by cyclic movements with a high degree of predictability. As such, the amount of kinematic variability can provide important information about a condition or an intervention that may affect the gait function . Three-dimensional gait analysis is a recognized method to assess changes in stride-to-stride variability associated with a medical condition or caused by an intervention. Thus, opioid induced changes in gait variability, and possible differences between opioid types, can be assessed objectively from differences in the variability of movements obtained from a three-dimensional gait analysis. The purpose of this study is to investigate differences in gait variability induced by two different single-dose opioid formulations and an inert placebo in healthy volunteers and knee osteoarthritis patients.

Detailed Description
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The study is designed as an experimental single center, double-blind treatment, cross-over study with inert placebo, Tapentadol (Palexia Depot), and Tramadolhydrochlorid (Mandolgin Retard), with a minimum of 7days wash-out periods. At day 1 (Visit 1), baseline measurements are carried out before tablet administration. Immediately after baseline measurements one tablet is administered, and hourly measurements are performed for 6 hours. Subsequently all participants enter a minimum 7 day washout period, after which they return to the facility to repeat the procedures at Visit 2 (day 8+) and Visit 3 (day 15+). The order of treatments will be randomized (1:1:1).

Official Title
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Opioid Induced Gait Variability

Conditions
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Opioid Induced Motor Disturbances

Intervention / Treatment
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* Drug: Tapentadol 50 mg Oral Tablet
* Drug: Tramadol Hydrochloride 100 mg Extended Release Oral Tablet
* Drug: Placebo Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects: In general good health, in the opinion of the Investigator, based on medical history and physical examination. Ability to comprehend and a willingness to provide written informed consent Age between 50 and 75 years No opioid usage 3 months prior to the study No musculoskeletal pain requiring medical attention during the previous 3 months Willing and able to complete study visits and procedures Willing to hold activity, exercise level, and concurrent treatments/therapies generally consistent during the study A body mass index (BMI) of ≤30 Patients with knee osteoarthritis (OA) Diagnosis of knee OA Ability to comprehend and a willingness to provide written informed consent Age between 50 and 75 years No opioid usage 3 months prior to the study Knee pain of at least 40 mm on a 0-100 mm visual analog scale (without analgesics) representing the average pain intensity during the previous week Willing to discontinue all pain medications 24 hours before and during examination visits Willing and able to complete study visits and procedures Willing to hold activity, exercise level, and concurrent treatments/therapies generally consistent during the study In general good health, in the opinion of the Investigator, based on medical history and physical examination. A body mass index (BMI) of ≤30 Exclusion Criteria: The same exclusion criteria apply for both healthy subjects and patients with knee osteoarthritis: Clinical signs of gait ataxia assessed by clinical neurological examination Independent or unsteady walking (i.e. dependence on walking device or stumbling gait) Counter indications to either of the investigational products, including but not restricted to: Allergy towards one or more of the investigational products or their excipient(s). Significant respiratory depression Current or serious asthma Hypercapnia Suspected or diagnosed paralytic ileus Acute intoxication by alcohol, hypnotica, centrally acting analgesics, psychopharmaca or other pharmaceuticals. Renal dysfunction Hepatic dysfunction Diseases of the biliary tract Acute pancreatitis Usage of monoamine oxidase inhibitors within the last 14 days Galactose intolerance Lactase deficiency Glucose/galactose malabsorption Epilepsy Previous usage of opioids without pain reliving effect. Patients who have a documented history of an allergic reaction or a clinically significant intolerance to opioids Malignant pain Excessive joint laxity in the lower extremities indicative of functional ligamentous deficiency. Dependency of walking aid (stick, cane, roller etc.). Positive Clock Drawing Test Abuse of alcohol, medicine and narcotics within past 5 years. History of symptoms of autoimmune disorders Diabetes Pregnancy or breast feeding History, diagnosis, or signs and symptoms of clinically significant neurological disease History, diagnosis, signs or symptoms of any clinically significant psychiatric disorder

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo oral tablet<br>One inert calcium tablet is administered after a set of baseline measurements are performed. Subsequently outcomes are assessed every hour for 6 hours, yielding a total of 7 hourly measurements. | Drug: Placebo Oral Tablet<br>* calcium tablet<br>* Other names: Calcium tablet;|
| Experimental: Tramadol Hydrochloride 100 mg Extended Release Oral Tablet<br>One tablet containing 100 milligrams (mg) Mandolgin Retard, Sandoz is administered after a set of baseline measurements are performed. Subsequently outcomes are assessed every hour for 6 hours, yielding a total of 7 hourly measurements. | Drug: Tramadol Hydrochloride 100 mg Extended Release Oral Tablet<br>* 1 tablet administered<br>* Other names: Mandolgin Retard (100 mg);|
| Experimental: Tapentadol 50 mg Oral Tablet<br>One tablet containing 50 milligrams (mg) Palexia Depot, Grünenthal is administered after a set of baseline measurements are performed. Subsequently outcomes are assessed every hour for 6 hours, yielding a total of 7 hourly measurements. | Drug: Tapentadol 50 mg Oral Tablet<br>* 1 tablet administered<br>* Other names: Palexia Depot (50 mg);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Gait variability | Three dimensional gait analysis during 6 minutes of continuous treadmill walking. | every hour from pre-tablet administration (hour 0) to hour 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Self reported dizziness | Current dizziness is assessed by means of a 100 mm visual analog scale | every hour from pre-tablet administration (hour 0) to hour 6 | 
| Self reported knee pain | Current knee pain is assessed by means of a 100 mm visual analog scale | every hour from pre-tablet administration (hour 0) to hour 6 |