HyperhydrosisPhase 1AIDES-GNCT01588717
Excessive Sweating Caused by Antidepressants: Measurement and Treatment With Glycopyrrolate (AIDES-G)
A Phase 1 study testing Glycopyrrolate in people with Hyperhydrosis and Depression, run by Thomas Jefferson University at 1 site in United States.
Trial summary
The study consists of measurement of antidepressant-induced excessive sweating and its treatment with an experimental medication, glycopyrrolate (approved to treat ulcers), which will be added to the antidepressant. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hyperhydrosis, Depression
- What is being tested?
- Glycopyrrolate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2012to Jun 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 years or older
- Presence of excessive sweating by self-report
- Within 2 months of initiation of an antidepressant or increase in the dose, there was a clear and substantial increase in sweating not explained by undue external warmth, exercise, or other reason. If treatment with the antidepressant was interrupted, did not persist for more than 6 weeks during that interruption
- Treatment with the antidepressant is deemed to be clinically necessary due to substantial benefit from the antidepressant that is causing the excessive sweating, and failure to respond to or tolerate an alternative antidepressant
- Decrease in dose of the antidepressant is either not clinically viable due to the benefit obtained at the current dose OR decrease in dose of the antidepressant has been tried but was not effective.
- Excessive sweating has persisted for at least 4 weeks prior to baseline assessment
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- The excessive sweating is rated by the patient as at least moderately bothersome.
- Episodes of excessive sweating occur at least twice a week for last 4 weeks
- Use of effective contraception (e.g., sterilization, oral contraceptives, condom with spermicide, etc)
Who cannot join
- Presence of another known disease that could potentially cause excessive sweating
- Failure to respond in the past to anticholinergic treatment for excessive sweating
- Previous allergic reaction to glycopyrrolate
- Narrow angle glaucoma
- Significant cardiac disease including cardiac or heart block
- Patients with known hot-flashes or who are menopausal
Show all 10Show fewer
- History of urinary retention
- History of seizures
- Pregnancy or breastfeeding
- Other significant medical illness or laboratory abnormalities that, in the judgment of the PI, would increase risk to the patient
Trial locations and contacts
1 site in 1 country.
United States1 site
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
About this study
Official title: A Pilot Study to Measure and Treat Antidepressant-Induced Excessive Sweating With Glycopyrrolate (AIDES-G)
The study consists of measurement of antidepressant-induced excessive sweating and its treatment with an experimental medication, glycopyrrolate (approved to treat ulcers), which will be added to the antidepressant. This is an open-label study (no placebo group or concealment of the nature of the treatment) that will last 8 weeks, including two weeks of baseline measurement without treatment with the study medication followed by six weeks of treatment with the study medication. The study is pilot study by Dr. Rajnish Mago that is based on the hypothesis that glycopyrrolate will be effective in reducing the severity of excessive sweating caused by antidepressant treatment, and will have minimal side-effects.
Read the detailed description
Sweating is a common and bothersome adverse effect of treatment with antidepressants. Tricyclics and selective serotonin reuptake inhibitors (SSRIs) have both been clearly shown to cause sweating. Increased sweating has been reported with venlafaxine (Pierre and Guze, 2000) and bupropion (Feighner et al. 1984) as well. It is unclear to what extent tolerance develops to antidepressant-induced sweating. It may continue to be a problem even after 6 or more months on the antidepressant (e.g., Mavissakalian et al., 2002).
The prevalence of sweating with SSRIs is estimated to be between 7% and 19% depending on the drug (Ashton \& Weinstein 2002). According to the Physician's Desk Reference, excessive sweating occurs in 3-11% patients in clinical trials of SSRIs. Considering the fairly high prevalence of excessive sweating during antidepressant use and its consequences of patient distress and treatment noncompliance, it is important that more intensive efforts be made to understand the phenomenon and to systematically study potential treatments for it.
The mechanism of antidepressant-induced sweating has not been clearly elucidated and there is no generally accepted treatment for it. Initially, a reduction in the dose may be attempted to resolve antidepressant-induced sweating. However, a reduction of dose may not always be helpful (Leeman, 1990; Ashton \& Weinstein 2002) as it has been noted that the presence of sweating is not a clear dose-related symptom. As well, reducing the dose of the antidepressant may lead to a worsening of depression and therefore be an unrealistic alternative.
Antiadrenergic drugs like clonidine and terazosin (Feder, 1995; Mago and Monti, 2007; Mago et al., 2009) may be effective for the treatment of antidepressant-induced excessive sweating because the nervous system control of sweating is initially mediated by adrenergic receptors. However, antiadrenergic treatment may be associated with a decrease in blood pressure in some patients, which may lead to dizziness, especially on standing up. Also, the improvement in excessive sweating may not be complete.
Therefore, additional approaches are needed. Sweat glands are innervated by nerve fibers that release acetylcholine. Anticholinergic medications could be used as a potential treatment for the excessive sweating. In case reports, the anticholinergic drug benztropine has been successfully used to treat antidepressant-induced excessive sweating (Garber and Gregory, 1997; Feder and Guze, 2000). However, this has not been confirmed in a clinical trial. Also, benztropine readily crosses the blood-brain barrier; therefore, in addition to its desired effect peripherally on the sweat glands, it tends to cause cognitive side effects through its central effects.
Glycopyrrolate is an anticholinergic medication that is preferred for a variety of clinical uses because it does not cross the blood-brain barrier to a great extent. It has been used for many years by anesthesiologists to dry secretions during surgical procedures. In a case series based on chart review (Tran et al., 2009), it was found to be effective for antidepressant-induced excessive sweating.
- Conditions
- Hyperhydrosis, Depression
- Being tested
- Glycopyrrolate
- Keywords
- Hyperhydrosis, Excessive Sweating, Sweating, Depression, Antidepressant
- Medical subject headings
- Hyperhidrosis, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GlycopyrrolateDrug
Also called Cuvposa®, Robinul®, Robinul® Forte
glycopyrrolate 2 to 6mg/day
| Study group | Role | What they receive |
|---|---|---|
| glycopyrrolate | Experimental | glycopyrrolate 2 to 6 mg/day Receives: Drug: Glycopyrrolate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Global Impression- Improvement scores
The main comparison will be the end-of-study mean v. the baseline mean
Measured: 9 weeks per subject
Secondary outcomes (1)
change in mean of patient rated severity of sweating for each week, and change in mean skin conductance for each week
Measured: 9 weeks per subject
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2012 (estimated)
- Study startApr 2012
- Primary completionJun 2016
- Study completionJun 2016
Why it stopped: PI left institution
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HyperhydrosisStudies of the same condition, open and under way.
- More trials run by Thomas Jefferson UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Thomas Jefferson University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Rajnish Mago, MD, Principal investigator, Thomas Jefferson University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01588717
- Sponsor's protocol ID
- AIDES-G
- Acronym
- AIDES-G
- Status last verified
- Aug 2016
- First submitted
- 26 Apr 2012
- Last updated
- 25 Aug 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study to Measure and Treat Antidepressant-Induced Excessive Sweating With Glycopyrrolate (AIDES-G)
- ClinicalTrials.gov ID
- NCT01588717
- Acronym / sponsor ID
- AIDES-G / AIDES-G
- Conditions
- Hyperhydrosis, Depression
- Keywords
- Hyperhydrosis, Excessive Sweating, Sweating, Depression, Antidepressant
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: PI left institution
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Thomas Jefferson UniversityUniversity, hospital or other
- Study start
- Apr 2012
- Primary completion
- Jun 2016 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 1 May 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study consists of measurement of antidepressant-induced excessive sweating and its treatment with an experimental medication, glycopyrrolate (approved to treat ulcers), which will be added to the antidepressant. This is an open-label study (no placebo group or concealment of the nature of the treatment) that will last 8 weeks, including two weeks of baseline measurement without treatment with the study medication followed by six weeks of treatment with the study medication. The study is pilot study by Dr. Rajnish Mago that is based on the hypothesis that glycopyrrolate will be effective in reducing the severity of excessive sweating caused by antidepressant treatment, and will have minimal side-effects.
Detailed description
Sweating is a common and bothersome adverse effect of treatment with antidepressants. Tricyclics and selective serotonin reuptake inhibitors (SSRIs) have both been clearly shown to cause sweating. Increased sweating has been reported with venlafaxine (Pierre and Guze, 2000) and bupropion (Feighner et al. 1984) as well. It is unclear to what extent tolerance develops to antidepressant-induced sweating. It may continue to be a problem even after 6 or more months on the antidepressant (e.g., Mavissakalian et al., 2002).
The prevalence of sweating with SSRIs is estimated to be between 7% and 19% depending on the drug (Ashton \& Weinstein 2002). According to the Physician's Desk Reference, excessive sweating occurs in 3-11% patients in clinical trials of SSRIs. Considering the fairly high prevalence of excessive sweating during antidepressant use and its consequences of patient distress and treatment noncompliance, it is important that more intensive efforts be made to understand the phenomenon and to systematically study potential treatments for it.
The mechanism of antidepressant-induced sweating has not been clearly elucidated and there is no generally accepted treatment for it. Initially, a reduction in the dose may be attempted to resolve antidepressant-induced sweating. However, a reduction of dose may not always be helpful (Leeman, 1990; Ashton \& Weinstein 2002) as it has been noted that the presence of sweating is not a clear dose-related symptom. As well, reducing the dose of the antidepressant may lead to a worsening of depression and therefore be an unrealistic alternative.
Antiadrenergic drugs like clonidine and terazosin (Feder, 1995; Mago and Monti, 2007; Mago et al., 2009) may be effective for the treatment of antidepressant-induced excessive sweating because the nervous system control of sweating is initially mediated by adrenergic receptors. However, antiadrenergic treatment may be associated with a decrease in blood pressure in some patients, which may lead to dizziness, especially on standing up. Also, the improvement in excessive sweating may not be complete.
Therefore, additional approaches are needed. Sweat glands are innervated by nerve fibers that release acetylcholine. Anticholinergic medications could be used as a potential treatment for the excessive sweating. In case reports, the anticholinergic drug benztropine has been successfully used to treat antidepressant-induced excessive sweating (Garber and Gregory, 1997; Feder and Guze, 2000). However, this has not been confirmed in a clinical trial. Also, benztropine readily crosses the blood-brain barrier; therefore, in addition to its desired effect peripherally on the sweat glands, it tends to cause cognitive side effects through its central effects.
Glycopyrrolate is an anticholinergic medication that is preferred for a variety of clinical uses because it does not cross the blood-brain barrier to a great extent. It has been used for many years by anesthesiologists to dry secretions during surgical procedures. In a case series based on chart review (Tran et al., 2009), it was found to be effective for antidepressant-induced excessive sweating.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| glycopyrrolate | Experimental | Drug: Glycopyrrolateglycopyrrolate 2 to 6 mg/day |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age 18 years or older
- Presence of excessive sweating by self-report
- Within 2 months of initiation of an antidepressant or increase in the dose, there was a clear and substantial increase in sweating not explained by undue external warmth, exercise, or other reason. If treatment with the antidepressant was interrupted, did not persist for more than 6 weeks during that interruption
- Treatment with the antidepressant is deemed to be clinically necessary due to substantial benefit from the antidepressant that is causing the excessive sweating, and failure to respond to or tolerate an alternative antidepressant
- Decrease in dose of the antidepressant is either not clinically viable due to the benefit obtained at the current dose OR decrease in dose of the antidepressant has been tried but was not effective.
Key exclusion criteria (10 listed)
- Presence of another known disease that could potentially cause excessive sweating
- Failure to respond in the past to anticholinergic treatment for excessive sweating
- Previous allergic reaction to glycopyrrolate
- Narrow angle glaucoma
- Significant cardiac disease including cardiac or heart block
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GlycopyrrolateAlso: Cuvposa®, Robinul®, Robinul® Forteglycopyrrolate 2 to 6mg/day | Drug | glycopyrrolate |
Primary outcome
Clinical Global Impression- Improvement scores
Time frame: 9 weeks per subject
The main comparison will be the end-of-study mean v. the baseline mean
1 secondary outcome
change in mean of patient rated severity of sweating for each week, and change in mean skin conductance for each week
Time frame: 9 weeks per subject
Results and safety
The study was stopped early (reason given: PI left institution). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rajnish Mago, MD principal investigator
Thomas Jefferson University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Glycopyrrolate in people with Hyperhydrosis and Depression, run by Thomas Jefferson University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 25 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: PI left institution). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical Global Impression- Improvement scores (time frame: 9 weeks per subject). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Aug 2016.