Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT01182766 |
| Other study ID # |
15597 |
| Secondary ID |
5R01AA019720-02 |
| Status |
Active, not recruiting |
| Phase |
Phase 2/Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
September 2011 |
| Est. completion date |
June 2022 |
Study information
| Verified date |
May 2022 |
| Source |
University of Virginia |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
This research study aims to test whether topiramate (a drug that is being used for seizure)
will help individuals who have problems with both alcohol and nicotine. The investigators
believe that individuals taking topiramate will be more successful at abstaining from both
alcohol and nicotine than individuals taking placebo.
Description:
We propose a novel pharmacological strategy for treating alcohol and nicotine dependence
concomitantly.
The reinforcing effects of both alcohol and nicotine are mediated through the
cortico-mesolimbic dopamine (CMDA) system, and the concomitant use of both drugs enhances
their pharmacological effects. We propose a better approach to control dopamine (DA) effects
by contemporaneous indirect modulation of DA release and its functional expression. Both DA
release from its cell bodies in the ventral tegmental area and the expression of its
reinforcing effects through the cortico-mesolimbic system are modulated by GABA efferents
under the tonic control of glutamate-mediated excitatory amino acid pathways. Thus, it is
reasonable to hypothesize that a medication that facilitates cortico-mesolimbic GABAergic
function and inhibits glutamate action should diminish both nicotine's and alcohol's
reinforcing effects by inhibiting the release of midbrain DA and its functional expression
through pathways projecting from the nucleus accumbens to the cortex. The promise of this
novel approach is exemplified by our recent proof-of-concept demonstration that topiramate
compared with placebo significantly improved smoking abstinence rates and decreased serum
cotinine levels among alcohol dependent smokers. An important clinical effect of topiramate
in alcohol-dependent individuals appears to be that its anti-withdrawal effects promote the
gradual tapering of drinking. Hence, due to this unique anti-withdrawal effect of topiramate,
we propose to adopt the same methodology for treating alcohol-dependent individuals, as is
common practice with smokers, of setting a target quit date (TQD) after which relapse to
either drug can be measured. We propose an 18-week, double-blind clinical trial with
follow-up visits at 1 month and 3 months, in which alcohol-dependent smokers will receive
brief behavioral compliance enhancement treatment (BBCET) plus a smoking self-help manual as
their psychosocial treatment, and will be randomized to receive placebo,high-dose topiramate
(up to 250 mg/day), or low-dose topiramate (up to 125 mg/day) to prevent relapse to heavy
drinking and smoking. Each of the 3 treatment arms shall contain 98 individuals, with a total
N of 294.
The TQD will occur at the beginning of the 6th week of treatment. Our primary objective is to
determine whether both low- and high-dose topiramate will be more efficacious than placebo at
reducing the percentage of heavy drinking days and increasing the continuous abstinence rate
for smoking determined by a combination of self-report and CO monitoring after the TQD and in
the last 4 weeks of treatment. We also will be able to determine whether a lower dose of
topiramate is as efficacious as the higher dose and, therefore, is associated with a lower
adverse profile. Our secondary objectives are to test whether topiramate will be more
efficacious than placebo at improving quality of life and reducing craving after the TQD and
in the last 4 weeks of treatment and whether this improvement will be sustained in the
follow-up phase.
