Joint Injections for Osteoarthritic Knee Pain

• ClinicalTrials.gov Identifier: NCT00085722
• Recruitment Status: Completed
• First Posted: June 16, 2004
• Last Update Posted: February 15, 2019
• Sponsor: University of Wisconsin, Madison
• Collaborator: National Center for Complementary and Integrative Health (NCCIH)
• Information provided by (Responsible Party): University of Wisconsin, Madison

Tracking Information

• First Submitted Date: June 14, 2004
• First Posted Date: June 16, 2004
• Last Update Posted Date: February 15, 2019
• Study Start Date: July 2004
• Actual Primary Completion Date: November 1, 2008 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: October 3, 2007): Quality of life, pain scores and disability at wks 0, 5, 9, 12, 24, 52 [ Time Frame: Participants will be followed for one year. ]
• Original Primary Outcome Measures: Not Provided
• Current Secondary Outcome Measures (submitted: October 30, 2012): Secondary outcomes include disease and general quality of life indicators (all subjects) and magnetic resonance image (in a subset of 37 subjects). [ Time Frame: Participants will be monitored for one year. ]
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Joint Injections for Osteoarthritic Knee Pain
• Official Title: The Efficacy of Prolotherapy in Osteoarthritic Knee Pain
• Brief Summary: The purpose of this study is to determine whether prolotherapy (PrT), a therapy based on injection of a sugar solution in and around the knee, can decrease pain and disability from knee osteoarthritis (OA).

Detailed Description

OA is a common, debilitating condition for which there is no cure and no known cause. Prolotherapy (PrT) is an injection-based therapy for chronic musculoskeletal pain in which an irritant solution is injected at painful ligaments and tendons to produce stronger connective tissue and decrease pain. Although limited studies suggest PrT is effective may be effective for low back pain, its use has not been rigorously studied in human clinical trials for osteoarthritis.

Participants in this study will be randomly assigned to receive one of three treatments: standard PrT, injections with a saline placebo, or a pamphlet with recommendations for home knee physical therapy. Injections will be given at Weeks 1, 5, and 9; injection group subjects will have the option to receive an additional 2 sets of injections. All participants will be assessed for a total of 1 year. A set of disease-specific and general quality-of-life questionnaires will be used to assess participants' outcomes . A randomized subset of participants (N=38)will receive magnetic resonance imaging (MRI)of the knee at baseline and 52 weeks. At study completion, participants who did not receive PrT will have the option to receive up to five sessions of PrT at no cost. Data will be collected for this group (minus MRI) and will be analyzed separately. Enrollment is limited to residents of Southern Wisconsin.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Osteoarthritis

Intervention

• Procedure: Dextrose Prolotherapy
  Injection procedure: 50% dextrose is diluted with .9% 'normal' saline and 1% lidocaine to achieve 15% dextrose for ligament injections and 25% dextrose for intra-articular injection.
  Other Name: Dextrose
• Procedure: Saline Prolotherapy
  7 mL 9% 'normal' saline and 3mL 1% lidocaine
  Other Name: Saline
• Other: At-home physical therapy exercise group
  Subjects in the at-home physical therapy exercise group will receive a patient information pamphlet about knee osteoarthritis and conservative care instructions for standard at-home physical therapy exercises
  Other Name: Exercise

Study Arms

• Experimental: Dextrose
  Subjects in Group 1 receive PrT with 15% and 25% dextrose solution, as it is generally practiced in the US today.
  Intervention: Procedure: Dextrose Prolotherapy
• Placebo Comparator: Normal saline
  Subjects in Group 2 will receive the same treatment as Group 1, except that a 0.9% 'normal' saline solution with no known benefit will be used instead of dextrose.
  Intervention: Procedure: Saline Prolotherapy
• Exercise
  At-home physical therapy exercises as a non-injection control
  Intervention: Other: At-home physical therapy exercise group

Publications *

• Rejeski WJ, Ettinger WH Jr, Shumaker S, Heuser MD, James P, Monu J, Burns R. The evaluation of pain in patients with knee osteoarthritis: the knee pain scale. J Rheumatol. 1995 Jun;22(6):1124-9.
• Reeves KD, Hassanein K. Randomized, prospective, placebo-controlled double-blind study of dextrose prolotherapy for osteoarthritic thumb and finger (DIP, PIP, and trapeziometacarpal) joints: evidence of clinical efficacy. J Altern Complement Med. 2000 Aug;6(4):311-20. doi: 10.1089/10755530050120673.
• Eberle E, Ottillinger B. Clinically relevant change and clinically relevant difference in knee osteoarthritis. Osteoarthritis Cartilage. 1999 Sep;7(5):502-3. doi: 10.1053/joca.1999.0246. No abstract available.
• Klein RG, Eek BC, DeLong WB, Mooney V. A randomized double-blind trial of dextrose-glycerine-phenol injections for chronic, low back pain. J Spinal Disord. 1993 Feb;6(1):23-33.
• Ongley MJ, Klein RG, Dorman TA, Eek BC, Hubert LJ. A new approach to the treatment of chronic low back pain. Lancet. 1987 Jul 18;2(8551):143-6. doi: 10.1016/s0140-6736(87)92340-3.
• Dechow E, Davies RK, Carr AJ, Thompson PW. A randomized, double-blind, placebo-controlled trial of sclerosing injections in patients with chronic low back pain. Rheumatology (Oxford). 1999 Dec;38(12):1255-9. doi: 10.1093/rheumatology/38.12.1255.
• Yelland MJ, Glasziou PP, Bogduk N, Schluter PJ, McKernon M. Prolotherapy injections, saline injections, and exercises for chronic low-back pain: a randomized trial. Spine (Phila Pa 1976). 2004 Jan 1;29(1):9-16; discussion 16. doi: 10.1097/01.BRS.0000105529.07222.5B.
• Hackett GS, Hemwall GA, Montgomery GA. Ligament and Tendon Relaxation Treated by Prolotherapy. Fifth Ed. ed. Oak Park: Gustav A. Hemwall, 1993
• Linetsky FS, FRafael M,. Pain Management, 2002:381-402.
• Dorman TA. Prolotherapy: A survey. The Journal of Orthopaedic Medicine 1993;15(2):49-50
• Reeves KD, Hassanein K. Randomized prospective double-blind placebo-controlled study of dextrose prolotherapy for knee osteoarthritis with or without ACL laxity. Altern Ther Health Med. 2000 Mar;6(2):68-74, 77-80.
• Rogers WH, Wittink H, Wagner A, Cynn D, Carr DB. Assessing individual outcomes during outpatient multidisciplinary chronic pain treatment by means of an augmented SF-36. Pain Med. 2000 Mar;1(1):44-54. doi: 10.1046/j.1526-4637.2000.99102.x.
• Rabago D, Patterson JJ, Mundt M, Zgierska A, Fortney L, Grettie J, Kijowski R. Dextrose and morrhuate sodium injections (prolotherapy) for knee osteoarthritis: a prospective open-label trial. J Altern Complement Med. 2014 May;20(5):383-91. doi: 10.1089/acm.2013.0225. Epub 2014 Mar 17.
• Rabago D, Patterson JJ, Mundt M, Kijowski R, Grettie J, Segal NA, Zgierska A. Dextrose prolotherapy for knee osteoarthritis: a randomized controlled trial. Ann Fam Med. 2013 May-Jun;11(3):229-37. doi: 10.1370/afm.1504. Erratum In: Ann Fam Med. 2013 Sep-Oct;11(5):480.
• Rabago D, Zgierska A, Fortney L, Kijowski R, Mundt M, Ryan M, Grettie J, Patterson JJ. Hypertonic dextrose injections (prolotherapy) for knee osteoarthritis: results of a single-arm uncontrolled study with 1-year follow-up. J Altern Complement Med. 2012 Apr;18(4):408-14. doi: 10.1089/acm.2011.0030.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 14, 2019): 98
• Original Enrollment (submitted: June 23, 2005): 111
• Actual Study Completion Date: May 1, 2016
• Actual Primary Completion Date: November 1, 2008 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Pain from knee osteoarthritis that has impacted life for 3 months to 10 years
• X-ray results indicating knee osteoarthritis

Exclusion Criteria:

• Knee osteoarthritis surgical candidate
• History of total knee joint repair
• Prior use of PrT
• Prior fracture of the knee joint
• Joint injection of steroids or other drugs within the past 3 months
• Rheumatoid or inflammatory arthritis
• Chronic use of narcotic medication
• Other chronic pain diagnoses
• diabetes mellitus
• Body mass index (BMI) greater than 45
• Unresolved litigation
• Pregnancy
• Co-morbidity that may interfere with the study

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00085722
• Other Study ID Numbers: H-2004-0112; K23AT001879-01 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: University of Wisconsin, Madison
• Original Responsible Party: Not Provided
• Current Study Sponsor: University of Wisconsin, Madison
• Original Study Sponsor: National Center for Complementary and Integrative Health (NCCIH)
• Collaborators: National Center for Complementary and Integrative Health (NCCIH)

Investigators

• Principal Investigator: David P. Rabago, MD; University of Wisconsin Dept of Family Medicine

• PRS Account: University of Wisconsin, Madison
• Verification Date: February 2019