Initial Submission – Arthritis Care and Research
Article Format: Contributions from the Field

One Week of Treatment with a Cetylated Fatty Acid Topical Cream Reduces Pain and Improves Functional Performance in Patients with Osteoarthritis of the Elbow and Wrist

William J. Kraemer, Ph.D.¹, Nicholas A. Ratamess, Ph.D.^1,2, Jeffrey M. Anderson,M.D.¹, Carl M. Maresh, Ph.D.¹, David P. Tiberio, Ph.D., PT¹, Michael E. Joyce, M.D.¹, Barry N. Messinger, M.D.¹, Duncan N. French, M.S.¹,Matthew J. Sharman, M.S.¹, Martyn R. Rubin, Ph.D.¹, Ana L. Gómez, M.S.¹, Jeff S. Volek, Ph.D., R.D.¹, and Robert L. Hesslink Jr., Ph.D.³

¹Human Performance Laboratory, Department of Kinesiology and School of Medicine University of Connecticut, Storrs, CT 06269-1110

²Department of Health and Exercise Science The College of New Jersey, Ewing, NJ 08628

³Imagenetix, Inc., San Diego, CA 92127Running Footline: Cetylated Fatty Acids and Osteoarthritis

Running Footline: Cetylated Fatty Acids and Osteoarthritis

Address for Correspondence to:
William J. Kraemer, Ph.D., Professor
Human Performance Laboratory
Department of Kinesiology –Unit 1110
The University of Connecticut
Storrs, CT 06269-1110
Tel: 860-486-6892
Fax: x6898 fax
Email format: William.Kraemer@.uconn.edu

ABSTRACT

Objective: This investigation was an extension of a previous study in our laboratory where we have shown one month of treatment with a topical cream consisting of cetylated fatty acids to be effective for reducing pain and improving functional performance in patients with osteoarthritis (OA) of the knee (Kraemer et al., in press, Journal of Rheumatology). Methods: In the present investigation, patients diagnosed with OA of the elbow (N = 8; age = 59.1 ± 18.2 yrs) and wrist (N = 10; age = 60.3 ± 16.8 yrs) were tested for pain and functional performance before and after one week of treatment with a topical cream consisting of a blend of cetylated fatty acids (IGX2004™)and menthol applied twice per day. Results: Significant improvements in dynamic (~22 and 24.5%, respectively) and isometric (~33 and 42%, respectively) local muscle endurance, as well as a reduction in pain were observed. Neither group demonstrated significant changes in grip strength or maximal force production. Conclusion: One week of treatment with a topical cream consisting of IGX2004™ and menthol is effective for reducing pain and improving functional performance in patients with OA of the elbow and wrist.

Key Indexing Terms: FATTY ACIDS, OSTEOARTHRITIS, PHYSICAL PERFORMANCE, QUALITY OF LIFE

INTRODUCTION
     Osteoarthritis (OA) is a progressive, degenerative joint disease estimated to affect more than 21 million individuals in the United States.¹ The most common symptoms are pain, stiffness, reduced joint range of motion (ROM), and limitations to normal activities of daily living such as getting up from a chair, walking, balance, and ascending/descending stairs.^2-4 Due to the debilitating effects of OA, there is a need for alternative treatments that benefit patients with OA without harmful side effects.

     One potential treatment is the use of oral and/or a topical blend of proprietary cetylated fatty acids (e.g. IGX2004™).^5,6 Cetylated monounsaturated fatty acids have been shown to provide protection against arthritis in rats.⁷ and have been shown to increase knee range of motion and reduce pain in patients with knee OA.⁵ We have recently reported that a topical cream consisting of IGX2004™ significantly reduced pain and improved physical function in patients with knee OA.⁶ In that study, we reported acute improvements in stair climbing ability, timed “up and go” performance, knee range of motion, and a reduction in pain within 30 min of the first treatment with this topical cream. Additional improvements were observed after 30 days (i.e., cream was applied twice per day) of treatment. However, we only examined patients with knee OA and the topical cream used was only in its developmental stage. Recently, menthol has been added to this topical cream. Menthol has been shown to possess analgesic properties thereby reducing the sensation of pain.⁸ Therefore, the present investigation was an extension of our previous research.⁶ In this study, our purpose was to examine the effects of a topical cream consisting of IGX2004™, along with the addition of menthol, on pain and functional performance in patients with OA of the elbow and wrist over the course of one week of treatment.

MATERIALS AND METHODS
     Experimental Approach to the Problem. This study was part of a much larger investigation. Using a placebo-controlled, double-blind study, we have recently shown the benefits of treatment with a topical cream consisting of IGX2004™.⁶ The purpose of the present study was to extend the findings of our previous work and provide further support for the use of IGX2004™ (i.e., and the addition of menthol) in treatment of OA. In order to examine the primary hypothesis of the present investigation, patients diagnosed with OA by a physician were assigned to an experimental group based upon the location of his/her OA (i.e., elbow or wrist). Each patient applied the cream to the affected area twice per day every day for one week and subsequently returned to the lab for post-study functional performance testing. The testing protocols consisted of assessments of grip strength, elbow ROM, muscle strength, endurance, and pain. Due to the significant improvements observed in our previous investigation with use of a topical cream consisting of IGX2004™⁶ (i.e., as well as the lack of significant changes occurring in a control group using a placebo cream) and the high test-retest reliability (R = 0.95 to 0.99) obtained with our assessments, we chose not to include a control group for the present study.

Patients and Consent. All patients selected for the present study were recruited in conjunction with local physicians. Each participant was informed of the benefits and risks of the investigation and subsequently signed an approved consent form in accordance with the guidelines of the university’s Institutional Review Board for use of human subjects. Osteoarthritis was diagnosed by the treating physicians and 18 patients (16 women and 2 men) were assigned to one of two groups: elbow OA (N = 8) or wrist OA (N = 10). Patient demographics were: 1) elbow OA: age = 59.1 ± 18.2 yrs; height = 158.9 ± 7.6 cm; body mass = 76.8 ± 13.4 kg; years with OA = 5.9 ± 7.0 yrs, and 2) wrist OA: age = 60.3 ± 16.8 yrs; height = 159. 1 ± 6.7 cm; body mass = 74.7 ± 14.4 kg; years with OA = 4.9 ± 5.8 yrs.

Functional Performance Measures. Patients were assessed for functional performance before and following the seven-day experimental period. For patients with elbow and wrist OA, the selection of assessments and sequence performed was: 1) grip strength, 2) peak isometric force of the elbow flexors at 90 o, 3) one-repetition maximum (1 RM) of the elbow flexors, 4) isometric local muscular endurance of the elbow flexors at 90 o, and 5) number of repetitions performed for the arm curl with a standard resistance. All patients participated in two familiarization sessions prior to initiating the study. All tests were administered by the same investigator to ensure standardization of the procedures and test-retest intra-class correlations producing reliabilities for all of the tests ranging from Rs = 0.95 to 0.99.

Upper-Extremity Assessments. Maximal grip strength for each hand was assessed with a hand-grip dynamometer. Peak isometric force of the elbow flexors was assessed using a linear-movement resistance exercise machine in conjunction with a force plate (Kistler Instrument Corporation, Amherst, NY). The resistance bar was set for each patient to correspond to an elbow angle of 90 o (measured with a plastic goniometer) and was loaded such that no movement of the bar was permitted once adjusted to proper position. Each patient exerted maximal isometric force to the bar and the subsequent ground reaction forces were recorded. Hand and foot positions were standardized and marked for each testing session. Using the same resistance exercise machine, the 1 RM arm curl was assessed. Each patient began with the elbows fully extended and proceeded to lift the bar in a full ROM. Increments of 2.5 kg were added to each set until the patient could no longer complete a full repetition. For the isometric endurance assessment, patients were positioned in the resistance exercise machine (identical to the peak isometric force assessment) with hands placed on the bar at an elbow angle of 90 o. A standard resistance of 50-60% of patients’ pre-study 1 RM was added to the bar and each patient was instructed to hold the weight at this position for as long as possible. Patient fatigue, excessive pain, and/or failure to maintain the proper elbow and wrist position were criteria for test termination. The total time the patient was able to maintain this position was recorded. For the dynamic muscular endurance assessment, a dumbbell was used (e.g., 5.5 kg for men, 3.6 kg for women) for the unilateral arm curl exercise. Each patient performed as many repetitions as possible with each arm in a full ROM. All testing was conducted by a certified strength and conditioning specialist who used great caution when monitoring patient performance.

Clinical Assessment

      Patients were assessed on clinical ROM of the elbow (i.e., for those with elbow OA only). Patients were asked to fully extend (i.e., relax) and flex the forearm while in a standing position. A goniometer was used to measure joint angles in both positions. The same investigator performed all measurements, which yielded test-retest reliability of 0.99. In addition, a 0 (no pain) to 4 (extreme pain) pain scale was used to estimate patient pain before and following the one-week treatment intervention.

Topical Cream and Application

      The topical cream consisted of a proprietary blend of cetylated fatty acid oils (IGX2004™: cetyl myristoleate, cetyl myristate, cetyl palmitoleate, cetyl laureate, cetyl palmitate, and cetyl oleate), PEG-100 Stearate, benzyl alcohol, lecithin, carbomer, potassium hydroxide, tocopheryl acetate, menthol, and olive oil (Imagenetix, Inc., San Diego, CA 92127).. Patients were instructed to apply a standardized amount of cream to either both elbows or wrists. Daily logs were completed to assure 100% compliance. In addition, patients were not taking additional arthritis medications, did not initiate any exercise programs, and were not permitted to practice the performance tests to prevent any training effects during the one-week experimental period.

Statistical Analyses

      Statistical evaluation of all data was accomplished using a paired T-test with appropriate alpha level correction. Statistical power for the various dependent variables was determined to be 0.80-0.85 for the sample size used at the 0.05 alpha level (nQuery Advisor® software, Statistical Solutions, Saugus, MA). Significance was set at P ≤ 0.05.

RESULTS

     The results of this study are presented in Tables 1 and 2. For patients with elbow and wrist OA, significant improvements were observed only in the local muscular endurance assessments (i.e., isometric endurance test and repetitions of the arm curl). No differences were observed in any strength or ROM measurements. In addition, perception of pain was reduced.

                                                                       Tables 1 and 2 about here

DISCUSSION

      The results of the present study support our previous research indicating that a topical cream consisting of IGX2004™ and menthol is effective for reducing pain and improving performance. Specifically, dynamic and isometric local muscle endurance was significantly enhanced and a significant reduction in pain was observed in patients with OA of the elbow and wrist.

      Few studies have examined various topical treatments for improving performance and reducing pain in individuals with OA of the elbow or wrist. Most studies have investigated non-surgical treatments such as analgesics, nonsteroidal anti-inflammatory drugs, glucosamine, and chondroitin sulfate supplementation. ^9,10 Although effective, side effects may occur with chronic use of analgesics and NSAIDs. ¹⁰ Thus, the development of topical treatments that produce no or minimal side effects is warranted. Recent studies have shown beneficial effects of herbal supplements and topical creams including capsaicin, piroxicam gel, articulin-F, willow bark, and phytodolor for reducing pain in patients with OA. ⁹ Gemmell et al. ¹¹ examined treatment with a topical cream consisting of several herbs in addition to capsaicin and menthol for 42 days and reported a 35-38% reduction in pain and stiffness in patients with OA of the hand and knee. The magnitude of pain reduction in that study was slightly greater than the average pain reductions reported with use of NSAIDs (i.e., 30%). ¹² In the present study, we reported a ~43% reduction in pain in patients with OA of the wrist and elbow after only one week of treatment with a topical blend of IGX2004™ and menthol. Although our methodology for the assessment of pain differed from previous investigations (i.e., direct comparisons can not be made), the results of the present investigation indicate that comparable reductions in pain are possible with treatment of a topical cream consisting of a blend of IGX2004™ and menthol.

      The measurement of hand grip strength has been used as one assessment of physical function in patients with OA of the hand and wrist. Grip strength has been shown to be compromised in patients with OA of the wrist ¹³ and hand. ¹⁴ The reduction in grip strength has been mediated, in part, by pain and this reduction occurs in proportion to the severity of OA. ¹⁴ Topical cream treatment (e.g., herbal formulas, capsaicin) periods of 1-3 months have had limited effects on grip strength in patients with OA despite reductions in pain. ^15,16 Our findings support these data as we did not report any changes in grip strength after only 1 week of treatment despite reductions in pain. Thus, it appears that other treatment modalities (i.e., exercise), in addition to treatment with a IGX2004™/menthol topical cream, may be necessary to restore hand grip strength in patients with OA.

      A unique aspect to the present investigation was our selection of assessments of local muscular endurance and strength in patients with elbow and wrist OA. No differences were observed in peak isometric or dynamic strength of the elbow flexors; however we did report significant improvements in local muscular endurance (e.g., dynamic repetitions completed and isometric time to exhaustion). It was not surprising that maximal muscle strength did not change. The present investigation was only one week in duration and this was not long enough to initiate such changes. In addition, no exercise interventions were used. Maximal strength improvements have been shown to be specific to the training stimulus; ¹⁷ and therefore would be unlikely to change despite reductions in pain. However, our data demonstrated that submaximal local muscular endurance was responsive to pain reductions. Dynamic muscular endurance (i.e., elbow flexion repetitions performed to exhaustion) improved by ~ 23% and isometric local muscular endurance increased by ~ 36%. Considering that normal activities of daily living rely very little on one’s maximal lifting ability, our data demonstrate improvements in functional performance (i.e., improved submaximal endurance) may be obtained with a topical treatment consisting of a blend of IGX2004™ and menthol in patients with OA of the elbow or wrist.

      Although maximal muscle force production and elbow ROM did not significantly improve, the reduction in pain and improvements in all assessments of submaximal local muscular endurance observed indicated the potential benefits of treatment with IGX2004™/menthol for improving physical function in the upper extremities. In summary, our data provide further support for the use of a topical cream consisting of a blend of IGX2004™ and menthol in the treatment of patients with OA of the elbow and wrist.

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Table 1. Pain and Performance Changes in Patients with Elbow OA during the One-Week Experimental Period.

* = P ≤ 0.05; R – right arm/hand; L – left arm/hand; ext – fully extended elbow position; 1 RM – one-repetition maximum; ISOM - isometric

Table 2. Pain and Performance Changes in Patients with Wrist OA during the One-Week Experimental Period.

* = P ≤ 0.05; R – right arm/hand; L – left arm/hand; 1 RM – one-repetition maximum; ISOM - isometric