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Protein Turnover in the Osteoarthritic Knee (KneeT)

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ClinicalTrials.gov Identifier: NCT03037294
Recruitment Status : Recruiting
First Posted : January 31, 2017
Last Update Posted : August 14, 2019
Sponsor:
Information provided by (Responsible Party):
Lex Verdijk, Maastricht University Medical Center

Brief Summary:

Rationale: Osteoarthritis (OA) of the knee is a common cause of pain and disability, especially in people over the age of 65. In the current health care system both conservative (e.g. intra-articular injections with corticosteroids) and surgical (total knee replacement, TKR) treatment are applied. Although frequently used, certain effects of these treatments on protein metabolism remain unclear. It is well known that maintenance of different tissues is determined by a dynamic balance between protein synthesis and breakdown rates, with temporary changes in either protein synthesis or breakdown allowing net protein accretion or loss. However, intra-articular injections with corticosteroids as a conservative treatment are thought to have several negative consequences thereby potentially affecting protein metabolism of different musculoskeletal tissues. In addition, though protein supplementation has shown to be an effective nutritional strategy in stimulating muscle protein synthesis, it remains unclear to what extent other musculoskeletal tissues are able to respond to dietary protein supplementation. Therefore, the current study assesses the impact of intra-articular corticosteroid injections and preoperative protein supplementation on protein synthesis in different musculoskeletal tissues of the knee.

Objective: To investigate the effect of preoperative protein supplementation and corticosteroid injections on Hoffa's fat pad, synovium, tendon, bone, muscle, ligament, menisci, and cartilage protein synthesis of the OA knee.

Study design: Randomized, parallel (three groups) study design. Each of the two intervention groups will be compared to the control group separately.

Study population: 36 adults (45-75 y) with OA of the knee undergoing TKR. Intervention: Intra-articular injection of betamethasone (2ml; 4mg/ml) and bupivacaine (8ml; 5mg/ml) or daily 40 g of pre-sleep protein two weeks before TKR, or no intervention.

Main study parameters/endpoints: Primary study parameters include protein synthesis rates and enrichments of Hoffa's fat pad, synovium, tendon, bone, muscle, ligament, menisci, and cartilage. Secondary parameters include whole-body protein synthesis, breakdown, oxidation, and net balance.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The risks involved in participating in this study are minimal. There are no potential effects known for the ingestion of protein. The corticosteroid injection is standard care in conservative treatment of osteoarthritis. Risks are small and limited to the knee itself, such as cartilage degeneration or joint destruction. Muscle biopsies and tissue collection will be performed during the surgical procedure.


Condition or disease Intervention/treatment Phase
Osteo Arthritis Knee Protein Metabolism Dietary Supplement: Preoperative protein supplementation Drug: Preoperative intra-articular corticosteroid injection Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 39 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Protein Turnover in the Osteoarthritic Knee; the Impact of Preoperative Protein Intake and Intra-articular Corticosteroid Injections
Actual Study Start Date : January 1, 2017
Estimated Primary Completion Date : August 30, 2019
Estimated Study Completion Date : December 30, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Steroids

Arm Intervention/treatment
No Intervention: Control group
Subjects in the control group will receive no intervention.
Experimental: Protein group
Subjects in the protein group will receive a daily 40 g pre-sleep protein supplement during the 2-week preoperative period.
Dietary Supplement: Preoperative protein supplementation
Daily 40 g of pre-sleep protein supplementation during 2-week preoperative period.

Experimental: Corticosteroid group
Subjects in the corticosteroid group will receive a single intra-articular corticosteroid injection in the affected knee on the first day of the 2-week preoperative period.
Drug: Preoperative intra-articular corticosteroid injection
Intra-articular injection of corticosteroid (combination of betamethasone and bupivacaine) 2 weeks before surgery.




Primary Outcome Measures :
  1. Change in tissue-specific protein synthesis rates [ Time Frame: Throughout the surgical procedure (stable isotope methodology) and during the 2-week preoperative period (D2O dosing methodology). ]
    Fractional synthetic rates calculated based on tissue-free, plasma, and protein-bound tracer enrichments using stable isotope methodology and D2O dosing methodology.



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Ages Eligible for Study:   45 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent
  • Male and female patients scheduled for total knee arthroplasty
  • BMI between 18.5-30 kg/m2
  • Age 45 - 75 years
  • Mentally competent, as judged by the treating physician
  • Functioning gastrointestinal tract, eligible for oral protein supplementation

Exclusion Criteria:

  • Corticosteroid injections less than 3 months prior to participation
  • Any medications know to affect protein metabolism (i.e. corticosteroids, non-steroidal anti-inflammatories, or prescription strength acne medications)
  • Lactose intolerance
  • Diabetes mellitus
  • Smoking
  • Alcohol abuse
  • Lateral menisectomy
  • Rheumatoid arthritis
  • Hypertension, blood pressure above 140/90 mmHg
  • Peripheral artery disease Fontaine III or IV
  • COPD GOLD III or IV
  • Pheynylketonuria
  • Surgical intervention in the past four weeks
  • Total parenteral nutrition at day of surgery
  • Neoadjuvant chemotherapy or radiotherapy
  • GFR <20 mL/min/1.73 m2
  • Osteoarthritis of the knee secondary to septic arthritis, osteonecrosis, fracture, OD, or malignant processes
  • Collagen disorders, e.g. Marfan and Ehler-Danlos
  • Any other medical condition that may interfere with the safety of the subjects or the outcome parameters, in the investigators judgement
  • Investigator's uncertainty about the willingness or ability of the subject to comply with the protocol instructions
  • Participation in any other studies involving investigational or marketed products concomitantly or within two weeks prior to entry into the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03037294


Contacts
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Contact: Joey Smeets, MSc, MD +31651363946 joey.smeets@maastrichtuniversity.nl

Locations
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Netherlands
Maastricht University Medical Center Recruiting
Maastricht, Netherlands, 6229ER
Contact: Joey Smeets, MSc, MD    +31651363946    joey.smeets@maastrichtuniversity.nl   
Sponsors and Collaborators
Maastricht University Medical Center

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Responsible Party: Lex Verdijk, Assistant Professor, Maastricht University Medical Center
ClinicalTrials.gov Identifier: NCT03037294     History of Changes
Other Study ID Numbers: 16-3-036
First Posted: January 31, 2017    Key Record Dates
Last Update Posted: August 14, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
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Osteoarthritis
Osteoarthritis, Knee
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases