DMPS is a metal chelator which is approved for use in Europe. While not an FDA-approved
drug in the US, it is easily obtained and administered by alternative health
practitioners to their patients. A formulation called 'TD DMPS' (transdermal DMPS) is in
use, despite the fact there is no published literature to support that the agent is
absorbed transdermally. The investigators hypothesis is that DMPS is not absorbed through
the skin. The investigators plan to apply TD DMPS to healthy volunteers and then test
serum for presence of DMPS. In addition the investigators will measure urinary mercury
concentrations pre and post DMPS application.

Transdermal Absorption of Dimercaptopropane-1-Sulfonate (DMPS) and Effect on Urinary Mercury Excretion

Toxicity

I. Background Information and Literature:

2,3-dimercaptopropane-1-sulfonate (DMPS) is a chelating agent that has been used for
years in Europe for treatment of poisoning by metals such as mercury, arsenic, and lead.
It is a water soluble analog of dimercaptopropanol (British anti-Lewisite, or BAL), which
is an FDA approved chelating agent administered via deep intramuscular injection. DMPS is
not FDA approved, but is approved in Europe and is available in Germany without a
prescription, as Dimaval. It is felt to have less toxicity than BAL, and unlike BAL, is
effective when administered orally(1).

A comprehensive review by Aposhian, et al (1) notes that DMPS has been studied since the
late 1950's in the Soviet Union and China and appears innocuous. This review mentions a
1979 study which followed 168 scleroderma patients receiving DMPS for 10 years. Some
patients experienced mild side effects such as minor allergic reaction (26 patients, none
with anaphylaxis), nausea (11 patients), vertigo (7 patients), weakness (4 patients), or
itching (3 patients). No renal toxicity was noted. Additionally, chelation therapy with
oral DMPS was found to be safe when used in a series of patients with methylmercury
toxicity from contaminated grain in Iraq in 1972 (2). It was also not associated with any
adverse effects when used to orally chelate lead poisoned children in Baltimore, Maryland
in 1985 (3). This 1985 study cites case series of DMPS being safely and effectively used
for treatment of lead poisoning and inorganic mercury poisoning as well.

DMPS showed no mutagenicity in the Ames salmonella microsome plate test.

Soviet studies showed that when their usual human dose of 5mg/kg IV was increased to
100mg/kg IV, ulceration or necrosis at the injection site was noted. Animal studies with
very large (50mg/kg) IV doses showed tremors, tachycardia, dyspnea, vomiting, and
defecation. Other animal studies, however, noted no behavioral, weight, or blood
composition changes in animals given 15 or 80mg/kg IV DMPS.

Animal and human data demonstrated DMPS to be less toxic than the currently FDA approved
chelating agent, BAL (1).

Our study proposes to apply a single dose of a liquid formulation of DMPS to the skin.
Though there is no available animal or human data on this form of application, it is
being used throughout the U.S. by many naturopaths and physicians as a chelating agent
for children with autism. In the pamphlets and protocols of these physicians, the only
side effects they mention seeing are mild skin rash and, with chronic therapy, possible
depletion of other necessary metals (such as zinc and magnesium), for which they provide
a mineral supplement.

Since we will be using a small, one-time only dose, there is no risk of significant metal
or mineral depletion. The main risk to subjects will be mild skin rash, which can easily
be monitored.

II. Manufacturing information:

The transdermal DMPS to be used in the study will be obtained from Bellevue Pharmacy, a
compounding pharmacy (1034 S. Brentwood Blvd. Suite 102 St. Louis, MO 63117), which
supplies this product to doctors all over the U.S. According to the literature they
provide, the product is an anhydrous gel dispensed in 30 ml bottles. Each drop reportedly
contains 1mg of DMPS and 4mg of glutathione. We will buy the product we need for the
study in one bulk batch since each subject will only be getting one dose.

Prior to conducting the study, a bottle will be sent to the FDA lab to be analyzed for
confirmation of the presence of DMPS in the gel.

III. Investigator Qualifications:

Principal Investigator:

Anne-Michelle Ruha, MD, FACMT

Assistant Investigator:

Jennifer Smith, MD

Both investigators are board certified emergency physicians, Dr. Ruha is a board
certified medical toxicologist, and Dr. Smith is near completion of her fellowship in
medical toxicology (see attached curriculum vitae). At least one investigator will be
present at all times during the application of the product and the follow-up blood draws.
We will be prepared to deal with any acute reactions which occur, allergic or otherwise.
After this time period we will be available by phone via the poison center 24 hours a
day, 7 days a week for any concerns or complications experienced by study subjects.

IV. Study Protocol:

Since transdermal DMPS delivery is widely used but has not been studied, the clinical
question we wish to answer is whether DMPS is absorbed through the skin after transdermal
application and if so, whether it increases urinary mercury excretion.

We will recruit 10 healthy adult volunteers, over 18 years of age, who eat at least three
servings of fish per week (since this diet is associated with detectable levels of
mercury in the urine which may rise following chelation). Patients with known allergies
to DMPS or sulfa drugs or history of neurologic or renal disease will be excluded. We
will also control for number of mercury containing dental amalgams. History will be
obtained regarding any potential mercury exposures or recent vaccinations.

12 hr urine mercury and creatinine levels will be measured on all volunteers prior to any
treatment. The urine will be collected in acid-washed or heavy-metal-free specialty
containers. It will be refrigerated during and after the collection period and shipped to
NMS labs (with cooling pack) for measurement of mercury levels and mercury:creatinine
ratios. Each volunteer will then receive 120 mg of transdermal DMPS, applied to the bicep
area of one arm. The area of application will not exceed 2% body surface area. The dose
of DMPS was determined based on the "challenge dose" from the "Buttar Autism treatment
Protocol", used by Dr. Rashid Buttar in his clinic for the treatment of autistic
children. This protocol advises use of 3 mg/kg, with a max dose of 120 mg. After dosing,
urine will be collected for the next 12 hours (using the same protocol and send-out
procedure) and assayed for mercury and creatinine levels.

Additionally, after dosing, an intravenous catheter will be placed in the arm of each
subject for blood draws. Blood samples will be obtained at 30 minutes, 60 minutes, 90
minutes, 2 hours, 4 hours and 6 hours after application of the DMPS. These samples will
be sent to the FDA for DMPS analysis.

Subjects will be monitored during application and for the subsequent 6 hours for the
development of skin rash or any other symptoms related to the DMPS, though this is
unlikely. If rash develops the skin will be washed and the reaction can be treated as
necessary. At the end of the 6 hours, the skin will be cleansed with soap and water and
the treatment period ends.

When analyzing the data after collection, we will first look at whether any DMPS was
detectable in the blood after application. If so, we will examine the 12 hour urine
mercury levels from before and after application to determine whether this increased. We
will control for number of dental amalgams, which can affect baseline urinary Hg levels.
If an increase is detected, we will compare the magnitude of this increase to available
data on urinary Hg excretion increase after oral DMPS administration.

transdermal DMPS

Transdermal Absorption of DMPS and Its Effect on Urinary Mercury Excretion

We will recruit 10 healthy adult volunteers, over 18 years of age, who eat at least three
servings of fish per week (since this diet is associated with detectable levels of
mercury in the urine which may rise following chelation). Patients with known allergies
to DMPS or sulfa drugs or history of neurologic or renal disease will be excluded. We
will also control for number of mercury containing dental amalgams. History will be
obtained regarding any potential mercury exposures or recent vaccinations.

Transdermal Absorption of Dimercaptopropane-1-Sulfonate (DMPS) and Effect on Urinary Mercury Excretion

About this trial

Study ID

Status

Type

Phase

Placebo

Accepting

Trial Timing

What is this trial about?

What are the participation requirements?

Locations

Location

Status