Metabolic Complications Following Knee Injury in Young and Middle Aged Patients

Sedentary Lifestyle Clinical Trial

— OrthoMetKnee  

Official title:

Metabolic Complications Following Knee Injury in Young and Middle Aged Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02573662
• Other study ID #: AH-ORTHOMET-01
• Status: Recruiting
• Phase: N/A
• First received: March 13, 2015
• Last updated: November 8, 2015
• Start date: April 2015
• Est. completion date: June 2016

Study information

• Verified date: November 2015
• Source: Haugaard, Steen Bendix, M.D., DMSc
• Contact: Steen B Haugaard, MD, DMSc
• Phone: +45 53555066
• Email: sbhau[@]dadlnet.dk
• Is FDA regulated: No
• Health authority: Denmark: Danish Dataprotection Agency
• Study type: Observational

Clinical Trial Summary

Introduction This study evaluates the effect on glucose, lipid and bone metabolism following knee orthopedic procedures in healthy and physically active individuals. The sedentary rehabilitation period following these procedures may impact negatively on glucose, lipid and bone metabolic pathways, whereas the more physically active rehabilitation period instituted 6 weeks after surgery is hypothesized to impact positively.

Perspective This study will establish whether the well-known effects on glucose, lipid and bone metabolism of a sedentary lifestyle can be observed already following 6 weeks of physical inactivity in otherwise healthy and physically fit young and middle aged individuals. Investigators will thereby add knowledge to previous findings following strict bed-rest in healthy individuals on glucose, lipid and bone metabolism. In a clinical perspective it is important to examine the extent to which healthy individuals deteriorate in various metabolic pathways to better understand the pathophysiology behind these defects both in healthy individuals and in patients, who undergo bed rest or an equal reduction in physical activity as part of their rehabilitation.

Study design 16 physical active non-diabetic individuals of age 18 - 50 years who are undergoing knee surgical procedures at the Arthroscopic Center at Amager/Hvidovre Hospitals are recruited as cases for this case-control study.

10 non-diabetic control subjects matched for age, gender and physical activity are recruited to establish a reference level.

• The individuals will bring in morning spot urine for measurement of soluble urokinase plasminogen activating receptor (suPAR), creatinine, albumin and orosomucoid. Weight and height and waist and hip circumference will be measured.

• Oral glucose tolerance test (OGTT) with ingestion of 75 g glucose during 5 min from baseline (0 min). Plasma for glucose, insulin, C-peptide, non-esterified fatty acid (NEFA) will be drawn

• Before OGTT blood will be drawn for measurement of HbA1c, total cholesterol, LDL, HDL, triglyceride, Na, K, creatinine, hemoglobin (HgB), C-reactive protein (CRP), leukocytes, alanintransaminase (ALAT), alkaline phosphatase, Ca++, D vitamin, TSH, bone turnover markers (BTM), suPAR, interleukin 6 (IL6), TNFa, high-sensitivity C-reactive protein (hsCRP), lipid density profiling and lipid particle size.

• Dual energy X-ray absorptiometry (DXA) of hip, lumbar columna, visceral and subcutaneous fat is measured by Hologic Discovery scanner.

Description:

Hypothesis Implementation of a sedentary lifestyle with almost no physical activity in otherwise physical active individuals undergoing knee orthopaedic surgical procedures will during 6 weeks (4 to 8 weeks)

• derange insulin sensitivity and glucose effectiveness

• decrease disposition index

• imply hyper-secretion of incretin hormones and glucagon

• compensatory decrease in insulin clearance

• decrease lipid oxidation

• increase visceral adipose tissue

• increase number of low density lipoprotein particles and a decrease the particle size

• increase immune and low grade inflammatory response as measured in plasma and urine

• induce bone loss in hip as measured by bone mineral density (BMD)

• increase bone resorption and decrease bone formation as measured by selected bone turnover markers.

The proposed negative changes in bone, lipid and glucose metabolism are thought to reverse at least partly so, during active physical rehabilitation during week 6 through week 16.

Statistics Ten days of bed rest in 13 healthy young individuals showed a 20% (P<0.05) significant decrease in insulin sensitivity and a 50% (P<0.05) reduction in lipid oxidation. Thirty-one days of bed rest in 8 healthy women was significantly associated with bone loss in total hip (2.07%, P<0.001).

As the present study does not imply strict bed rest but exhibit a longer sedentary period of following up as the above studies and include a larger number of participants we are very likely to exhibit a power > 80% at significance level

Ethical issues The study is approved by the local scientific ethical committee and the Danish Data Protection Agency. The study adheres to the Danish Act on Processing of Personal Data and, Danish Act on Health and the Helsinki II convention of clinical trials. The study will be announced at the clinicaltrials.gov homepage. All participants are informed about the purpose of the study, all ethical issues and a written consent is obtained before participation.

Personal data from patient medical files will be accessed by principal investigator to gather information concerning the knee injuries in order to identify and characterize the knee injury for each subject. Personal data concerning demographic relations such as gender and age will be accessed as well to ensure the case subjects meet the inclusion criteria and for statistically use. To make assessments on study participation, the principal investigator will also gain access to relevant data from the patient s medical files concerning illnesses or conditions the case subject might report. The X-ray radiation from 1 DXA scan equals 1 day of background radiation in Denmark. Thus 3 DXA scans throughout the study period are equal to 3 days of background radiation. This amount of radiation is 30-fold less than that of a single standard CT-scan of abdomen. In other words the dose of radiation is so low that a calculation of risk is not possible.

The amount of blood drawn during the approximately 16 weeks of participation in the study is less than 500 ml, which is the standard amount of blood drawn at a single donation of blood from a blood donor. The use of intravenous cannula can cause irritation or infection of vein or insertion site. All procedures will be performed as described in SOP.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 16
• Est. completion date: June 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• Individuals of age 18 to 50 years

• Physically active >/= 1.5 hours/week up till baseline examination

• Physically active at least 2.5 hours/week before knee injury.

• The participants should undergo one of the following orthopaedic surgical procedures; Medial patella-femoral ligament (MPFL) surgery, Anterior Crusiate Ligament (ACL) and/or Posterior Crusiate Ligament (PCL) surgery, Knee Cartilage Injury surgery

• Informed written consent

Exclusion Criteria:

• BMI >/= 30 kg/m2

• Not physically active before surgical procedure as measured by questionnaire

• Known diabetes mellitus or HbA1c >/= 48 mol/mol

• Clinical significant anemia, liver or kidney disease as judged by the sponsor or principal investigator.

• Thyroid function abnormality (TSH < 0.1 or TSH > 10)

• Calcium metabolic derangement, Ca++ < 1.1 or Ca++ > 1.40

• Known osteoporosis

Inclusion/exclusion criteria for control subjects are similar except from surgical procedure

Study Design

Observational Model: Case Control, Time Perspective: Prospective

Related Conditions & MeSH terms

• Disease
• Glucose Metabolism Disorders
• Knee Injuries
• Lipid Metabolism Disorders
• Metabolic Diseases
• Sedentary Lifestyle

Intervention

Biological:
• Blood and Urine sampling
Blood and Urine Sampling

Radiation:
• DXA scan
Scan of Lumbar columna and neck of femur/hip Scan of visceral/subcutaneous fatty tissue

Biological:
• OGTT
Oral Glucose Tolerance Test for Minimal Model analysis for insulin sensitivity and Lipid oxidation

Locations

Country	Name	City	State
Denmark	Amager University Hospital	Copenhagen

Sponsors (2)

Lead Sponsor	Collaborator
Haugaard, Steen Bendix, M.D., DMSc	Hölmich, Per, M.D.

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in insulin sensitivity	Glucose metabolic: -insulin sensitivity as measured by MinModel-OGTT	Baseline to week 6	No
Secondary	Change in glucose metabolism	Change in beta-cell responsiveness compared to insulin sensitivity (disposition index); Change in glucose effectiveness; Change in insulin clearance; Change in visceral adipose tissue; Change in incretin secretion compared to insulin resistance and insulin secretion	Baseline to week 6 and to week 16	No
Secondary	Lipid metabolism	Change ind lipid oxidation as measured by MinModel-NEFA; Change in lipolysis; Change in rates of which NEFA leaves plasma pool	Baseline to week 6 and to week 16	No
Secondary	Bone Metabolism	BMD changes in total hip; changes in total BMD; change in lumbar BMD; changes in BTM of bone resorption (CTX) and formation (P1NP)	Baseline to week 6 and to week 16	No
Secondary	Atherosclerotic markers	change in low and high density lipoprotein particles and in particle size; changes in TNFa, IL6, hsCRP, suPAR and orosomucoid	Baseline to week 6 and to week 16	No
Secondary	Change in insulin sensitivity	Glucose metabolic: -insulin sensitivity as measured by MinModel-OGTT	week 6 and to week 16	No