This study is designed to determine whether a medicine that can produce temporary amnesia
(midazolam) can be used to block the memory of treatment with spinal manipulation. This is
important since any study that is designed to determine whether spinal manipulation is
effective would be better if patients were not aware of whether or not they were treated.
This would allow a true assessment of treatment effects without the complication of a strong
placebo effect that manipulative treatment may produce.
There has been growing recognition of the high frequency with which Americans utilize
complementary and alternative health care providers and that annually about 10% of the
population is treated by a chiropractor. While chiropractors employ several types of
treatment, spinal manipulation is the most important and unique of these therapies. Over
90% of the spinal manipulations performed in the U.S. are done by chiropractors with most of
the remainder performed by osteopathic physicians. The annual number of chiropractic visits
in the U.S. has been estimated at approximately 100 per 100 person-years.
Spinal manipulation and chiropractic have been controversial at least partially due to a
paucity of clinical scientific evidence of benefit. For example, reviews of the literature
on randomized clinical trials (RCT's) of manipulative treatment for back pain have variably
found evidence of benefit or insufficient evidence of benefit. A review of the existing
clinical trials of spinal manipulation for neck pain concluded that most of the five
existing RCT's were of relatively poor quality and that, despite some evidence for very
short-term benefit, studies of higher quality will be needed in order to determine whether
there is clinical benefit for this condition. This issue is important since neck pain is the
second most common reason for presentation to chiropractors.
There are several difficulties in researching the effects of spinal manipulation. Most of
the conditions that are treated (i.e., back and neck pain) do not have a well-defined
pathophysiology. Therefore, it is not possible to study treatment by evaluating the effects
of treatment on physiological variables. The lack of a proven pathophysiology also leads to
heterogeneous study populations with large variability in response to treatment. This makes
it necessary to use large experimental populations in order to detect any effects of
treatment. There is heavy reliance on subjective outcome measures in neck and back pain
research, making these clinical trials particularly sensitive to placebo or "nonspecific"
effects. The use of blinded subjects is the accepted method of dealing with these issues,
but blinding is particularly difficult to achieve when investigating physical interventions,
particularly those where the therapist can't be blinded as to whether s/he is delivering an
actual or sham treatment.
The present proposal is in response to a request for applications for pilot studies to
establish the methodological feasibility and strengthen the scientific rationale for
proceeding to full-scale RCTs on the use of chiropractic or osteopathy to manage or treat
musculoskeletal injuries and disorders. One of the stated goals of this request for
applications is to refine the control strategy for studies of manipulative therapy. The
proposed study will examine whether an amnestic agent, midazolam, can be used to blind
subjects to their experimental group in a double-blind, pilot RCT. This proposal is similar
to a study by Sloop et al who used diazepam to produce amnesia in a study of spinal
manipulation for chronic neck pain. The present study will utilize an agent with more
specific amnestic effects and will also address several methodological problems with their
study. If successful, the methods employed in this pilot study may permit a high degree of
blinding in full scale RCT's of spinal manipulation.
This study will enroll patients with chronic neck pain (more than 3 months duration) with
or without occipitally-based head pain and without signs of radiculopathy or myelopathy.
They must have pain of at least moderate intensity (by their report and by a score of at
least 3 out of 10 on a visual analogue pain scale) on at least four days out of a week and
have had some limitations of activity on a weekly basis due to their neck pain. These
subjects should not have had spinal manipulative treatment for at least two years and
should not have had any adverse reactions to manipulative treatment or to benzodiazepines.
They may not be regular users of benzodiazepine medications. They also should not be
currently enrolled in an ongoing physical therapy program, though they may be taking
analgesics, anti-inflammatories or other medications for their problem. They may continue
with any ongoing exercise program. Subjects will also be excluded if they are pregnant,
lactating or plan to be pregnant, if they have significant cardiac or pulmonary disease or
if they plan on relocating during the course of the study. The subjects will also be
evaluated by a trained and experienced manipulative practitioner (see below) for the
presence of lesions which would be amenable to manipulation and by a medical physician for
the absence of any contraindications to manipulative treatments.