Osteoarthritis of the Hands Clinical Trial
Official title:
The Analgesic Activity of a Topical Formulation in Patients With Osteoarthritis of the Hands
Osteoarthritis (OA) affects over 30 million people in the United States and represents our
nation's leading cause of disability. Data for the years between 1996-2005, indicate that OA
raised overall health care costs by $185.5 billion annually. Largely as a consequence of
this disease, the number of patients undergoing joint replacement surgery will quadruple
over the next 17 years. Importantly, several recent studies have demonstrated that OA is an
independent risk factor for cardiovascular disease . Presently investigators have no
medications that alter the natural history of OA. Weight control, exercise and some physical
therapy measures are the only interventions short of total joint replacement that alter the
course of this disease. To make matters worse, investigators have experienced only setbacks
in use of medications aimed at symptom control. Recognition of toxicities of non-steroidal
anti-inflammatory drugs (NSAIDs) and narcotic-based analgesics has narrowed the presently
available armamentarium for pain control in OA . Clearly OA is a major factor that demands
better solutions as the health care system is redesigned.
OA involving the hands represents a major part of the overall burden of this disease. In
radiographic surveys about a quarter of the total US population has changes consistent with
OA involving the hands. Among the elderly, radiographic hand OA has been found in over half
of such individuals and as many as a quarter of them suffer from pain and functional
incapacitation. The joints affected typically are the first carpometacarpal (CMC-1) joint,
the distal interphalangeal (DIP) joints, and the proximal interphalangeal (PIP) joints .
Therapeutic options include acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs),
and a variety of physical measures such as physical therapy, bracing, and heat and cold
applications. To achieve some symptomatic benefit while limiting systemic toxicity, topical
therapies have been developed which either act as counter irritants, seek to reduce
substance P (capsaicin), or to deliver an NSAID locally through the skin. The leading
example of the latter is Diclofenac sodium gel which was shown to reduce pain intensity and
improve hand function in a double blind controlled trial. However none of these measures
have proven sufficiently effective to meet patient needs. Topical polytherapy will be
employed in this study to see if it will be effective against the pain of OA.
A potentially more effective approach is to provide a combination of analgesic and
anti-inflammatory agents through a topical delivery system. In the present study compounds
with anti-inflammatory and analgesic properties will be combined in a vehicle that promotes
penetration of molecules through the skin to deeper underlying tissues such as the joint
capsule at articulations in the hands. The vehicle consists of Versapro cream base (a
formulation of Medisca, Inc. that contains Vitamin E and Aloe Vera, along with other
ingredients that are proprietary), Tranilast powder, Pentoxifylline USP powder, Cetyl
Myristoleate 40% wax, liquid Pentylene Glycol, liquid Dimethyl Sulfoxide (DMSO) USP, liquid
Propylene Glycol USP, liquid Ethoxy Diglycol reagent, liquid Ethyl Alcohol 190 proof USP.
These are all inert ingredients, i.e. they only promote penetration of molecules through the
skin. A mixture of the following compounds will be incorporated into this vehicle as the
active test medication:
Diclofenac 3% - an NSAID. FDA pregnancy category C for the first 30 weeks, then category D.
Baclofen 2% - an agonist for the GABAB receptors. FDA pregnancy category C.
Orphenadrine 5% - an anticholinergic drug of the ethanolamine antihistamine class. FDA
pregnancy category C.
Bupivacaine 2% - a local anesthetic that binds voltage-gated sodium channels and blocks
sodium influx into nerve cells preventing depolarization. FDA pregnancy category C.
Due to the FDA pregnancy categories for the drugs used in this study, pregnancy is an
exclusion criteria.
The control medication: The vehicle alone will serve as the control compound.
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Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment