Sjogren's SyndromeNCT00565526
Evaluation of the Role of the Autonomic Nervous System in Sj(SqrRoot)(Delta)Gren s Syndrome
An observational study of Sjogren's Syndrome and Dysautonomia, run by National Institute of Dental and Craniofacial Research (NIDCR) at 1 site in United States.
Trial summary
Background: Sj(SqrRoot)(Delta)gren s Syndrome (SS) is an autoimmune disease that affects the glands that produce saliva and tears, causing dry eyes and dry mouth. Researchers do not know the exact cause of SS, but they believe that it may be caused by abnormalities in the autonomic nervous system (ANS) that stimulate… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Sjogren's Syndrome, Dysautonomia
- How many people
- 28 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Nov 2007to 10 Apr 2014
- Phase
- Observational
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of primary Sjogren s syndrome based on American-European Consensus Group Sjogren s syndrome classification criteria or healthy volunteers.
- Both genders and all minorities.
- Age at entry at least 18 and less than 65 years.
Who cannot join
- Current use of medications known to significantly influence the activity of the sympathetic or parasympathetic nervous system if they cannot be held safely at the time of ANS testing
- Known co-existing diagnosis of ANS dysfunction (for healthy volunteers)
- Medications-requiring diabetes mellitus
- Diabetic autonomic neuropathy
- Vitamin B12, folate deficiency, requiring replacement
- Hepatic failure (AST or ALT greater than 1.5 x upper limit of normal)
Show all 18Show fewer
- Renal failure (GFR less than 30 ml/min, as estimated by the MDRD)
- Congestive heart failure (Class II-IV)
- Refractory ventricular arrhythmias
- Symptomatic coronary heart disease
- Previously established diagnosis of sinus node dysfunction
- Severe anemia (Hgb less than 8)
- Psychosis
- Pregnant or lactating women
- A candidate subject is excluded if, in the judgment of the Principal Investigator, protocol participation would place the subject at substantially increased acute medical risk.
- Not able to provide informed consent
- Medications: A candidate subject is excluded if clinical considerations require that the subject continue treatment with a drug likely to interfere with the scientific results i.e. a tricyclic antidepressant or fludrocortisone. Subjects with known or suspected allergy or hypersensitivity to any test drug are excluded from receiving that drug. Subjects who must take medications daily in the following categories are excluded: tricyclic antidepressants, beta blockers, barbiturates, if they cannot be safely held during testing. Subjects unable to discontinue nicotine or alcohol temporarily are excluded. Subjects are not to discontinue any medications before the subject or the subject s physician discusses this with the Principal Investigator, Dr. Nikolov, or the Associate Investigator, Dr. Goldstein. If it is decided that discontinuing medications would be unsafe, then the subject is excluded from the study. Subjects must discontinue use of alcohol and tobacco throughout the period of testing in the protocol.
- Herbal Medicines and Dietary Supplements: Certain herbal medicines or dietary supplements are known or suspected to interfere with the experimental results, and such herbal medicines or dietary supplements must be discontinued before enrollment in the study. For many herbal medicines or dietary supplements, the mechanisms of action and therefore the possible effects on the experimental results are unknown. In cases where the subjects wish to continue their herbal medicines or dietary supplements while on study, and search of the available medical literature fails to identify effects that are known or expected to interfere with the experimental results, then the subjects may participate.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Clinical and Laboratory Evaluation of the Autonomic Nervous System in Primary Sjogren's Syndrome
Background:
Sj(SqrRoot)(Delta)gren s Syndrome (SS) is an autoimmune disease that affects the glands that produce saliva and tears, causing dry eyes and dry mouth.
Read more
Researchers do not know the exact cause of SS, but they believe that it may be caused by abnormalities in the autonomic nervous system (ANS) that stimulate these glands.
Objectives:
To better understand ANS function in patients with SS.
To compare information about ANS function in healthy individuals and in patients with SS.
Eligibility:
Patients with Sj(SqrRoot)(Delta)gren s Syndrome who are 18 years of age and older, and who are not pregnant or breastfeeding.
Participants will be asked to taper or discontinue the use of certain medications or dietary supplements before the ANS testing.
Participants must be willing to discontinue the use of alcohol and tobacco 24 hours prior to testing.
Design:
The study will require one inpatient admission and/or outpatient visits to the NIH Clinical Center.
The following tests and procedures will be performed:
- Saliva, tear, and sweat production measurements to evaluate the function of glands.
- Testing of changes to the cardiovascular system, including blood pressure and blood flow testing, and an electrocardiogram designed to evaluate hemodynamic changes controlled by the ANS.
- Testing of changes to the gastrointestinal system, including a swallowing assessment study, barium swallow study, and gastric emptying study designed to evaluate gastrointestinal function controlled by the ANS.
- Tests to evaluate the ANS function in response to certain drugs (edrophonium, glucagon and acetylcholine).
- Self-reported questionnaire on ANS function and emotional/psychological well-being.
Additional procedures and tests may include the following:
- Blood samples.
- Optional skin biopsy to study sweat glands and nerve supply of the skin.
Read the detailed description
Sj(SqrRoot)(Delta)gren s syndrome (SjS) is a systemic exocrinopathy that affects as high as 5 percent of the population. It is manifested predominantly as dry eyes, dry mouth, and fatigue. The exocrinopathy can be encountered alone (primary SjS) in approximately one half of the patients or in the presence of another autoimmune disorder such as rheumatoid arthritis, systemic lupus erythematosus, or systemic sclerosis (secondary SjS). The most widely accepted classification for SjS is the American-European consensus classification criteria for SjS.(Vitali, Bombardieri et al. 2002)
Current understanding about the pathogenesis of SjS stems from the assumption that the autoimmune destruction of the exocrine glands leads to their hypofunction and symptoms of dryness. The existing evidence however does not fully support this assumption and cannot explain the underlying pathogenic mechanisms of SjS for the following reasons: 1) Discordance between severely affected function and abundance of histologically normal and ex vivo functional salivary glands; 2) at least 20% of patients have no evidence of systemic autoimmunity; 3) Animal models of SjS develop glandular dysfunction long before they develop autoimmunity; 4) Dryness and related symptoms respond poorly to immunosuppressive, including newer biologics, but fairly well to secretagogues such as pilocarpine. 5) No pathogenic antibodies or target epitopes have been identified to date to unify the pathogenesis of the syndrome.
All exocrine glands are innervated by the autonomic nervous system (ANS) and dysautonomia can mimic the phenotype of SjS, particularly cardinal manifestations, such as xerostomia and xerophthalmia. Thus we hypothesize that ANS dysfunction is central to the pathogenesis of SjS and propose to systematically study the ANS function in our cohort of patients with primary SjS compared with normative data from age and sex-matched controls. This protocol calls for a comprehensive evaluation of autonomic function, using physiological, neuropharmacologic, neurochemical, and imaging approaches, to identify consistent distinctive patterns of ANS involvement in SjS and thereby improve the diagnosis and understanding of pathophysiologic mechanisms of SjS.
- Conditions
- Sjogren's Syndrome, Dysautonomia
- Keywords
- Autonomic Nervous System, Sjogren's Syndrome, Pathogenesis, Cholinergic, Parasympathetic, Sjogren Syndrome
- Medical subject headings
- Sjogren's Syndrome, Autonomic Nervous System Diseases
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2007 (estimated)
- Study start26 Nov 2007
- Study completion10 Apr 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Sjogren's SyndromeStudies of the same condition, open and under way.
- 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
- Observational
- Time perspective
- Prospective
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Dental and Craniofacial Research (NIDCR)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Stamatina J Danielides, M.D., Principal investigator, National Institute of Dental and Craniofacial Research (NIDCR)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00565526
- Sponsor's protocol ID
- 080018
- Other IDs
- 08-D-0018
- Status last verified
- 10 Apr 2014
- First submitted
- 29 Nov 2007
- Last updated
- 5 Jul 2018
- Results posted
- No
Publications
Sharma RV, Mathur SN, Ganguly J. Studies on the relative biopotencies and intestinal absorption of different apo-beta-carotenoids in rats and chickens. Biochem J. 1976 Aug 15;158(2):377-83. doi: 10.1042/bj1580377.
PubMed 985434Arbuckle MR, McClain MT, Rubertone MV, Scofield RH, Dennis GJ, James JA, Harley JB. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med. 2003 Oct 16;349(16):1526-33. doi: 10.1056/NEJMoa021933.
PubMed 14561795Bjorklund H, Dalsgaard CJ, Jonsson CE, Hermansson A. Sensory and autonomic innervation of non-hairy and hairy human skin. An immunohistochemical study. Cell Tissue Res. 1986;243(1):51-7. doi: 10.1007/BF00221851.
PubMed 2417723Imrich R, Alevizos I, Bebris L, Goldstein DS, Holmes CS, Illei GG, Nikolov NP. Predominant Glandular Cholinergic Dysautonomia in Patients With Primary Sjogren's Syndrome. Arthritis Rheumatol. 2015 May;67(5):1345-52. doi: 10.1002/art.39044.
PubMed 25622919
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical and Laboratory Evaluation of the Autonomic Nervous System in Primary Sjogren's Syndrome
- ClinicalTrials.gov ID
- NCT00565526
- Acronym / sponsor ID
- 080018
- Conditions
- Sjogren's Syndrome, Dysautonomia
- Keywords
- Autonomic Nervous System, Sjogren's Syndrome, Pathogenesis, Cholinergic, Parasympathetic, Sjogren Syndrome
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- National Institute of Dental and Craniofacial Research (NIDCR)US National Institutes of Health
- Study start
- 26 Nov 2007
- Study completion
- 10 Apr 2014
- First posted
- 30 Nov 2007 (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.
Background:
Sj(SqrRoot)(Delta)gren s Syndrome (SS) is an autoimmune disease that affects the glands that produce saliva and tears, causing dry eyes and dry mouth.
Researchers do not know the exact cause of SS, but they believe that it may be caused by abnormalities in the autonomic nervous system (ANS) that stimulate these glands.
Objectives:
To better understand ANS function in patients with SS.
To compare information about ANS function in healthy individuals and in patients with SS.
Eligibility:
Patients with Sj(SqrRoot)(Delta)gren s Syndrome who are 18 years of age and older, and who are not pregnant or breastfeeding.
Participants will be asked to taper or discontinue the use of certain medications or dietary supplements before the ANS testing.
Participants must be willing to discontinue the use of alcohol and tobacco 24 hours prior to testing.
Design:
The study will require one inpatient admission and/or outpatient visits to the NIH Clinical Center.
The following tests and procedures will be performed:
- Saliva, tear, and sweat production measurements to evaluate the function of glands.
- Testing of changes to the cardiovascular system, including blood pressure and blood flow testing, and an electrocardiogram designed to evaluate hemodynamic changes controlled by the ANS.
- Testing of changes to the gastrointestinal system, including a swallowing assessment study, barium swallow study, and gastric emptying study designed to evaluate gastrointestinal function controlled by the ANS.
- Tests to evaluate the ANS function in response to certain drugs (edrophonium, glucagon and acetylcholine).
- Self-reported questionnaire on ANS function and emotional/psychological well-being.
Additional procedures and tests may include the following:
- Blood samples.
- Optional skin biopsy to study sweat glands and nerve supply of the skin.
Detailed description
Sj(SqrRoot)(Delta)gren s syndrome (SjS) is a systemic exocrinopathy that affects as high as 5 percent of the population. It is manifested predominantly as dry eyes, dry mouth, and fatigue. The exocrinopathy can be encountered alone (primary SjS) in approximately one half of the patients or in the presence of another autoimmune disorder such as rheumatoid arthritis, systemic lupus erythematosus, or systemic sclerosis (secondary SjS). The most widely accepted classification for SjS is the American-European consensus classification criteria for SjS.(Vitali, Bombardieri et al. 2002)
Current understanding about the pathogenesis of SjS stems from the assumption that the autoimmune destruction of the exocrine glands leads to their hypofunction and symptoms of dryness. The existing evidence however does not fully support this assumption and cannot explain the underlying pathogenic mechanisms of SjS for the following reasons: 1) Discordance between severely affected function and abundance of histologically normal and ex vivo functional salivary glands; 2) at least 20% of patients have no evidence of systemic autoimmunity; 3) Animal models of SjS develop glandular dysfunction long before they develop autoimmunity; 4) Dryness and related symptoms respond poorly to immunosuppressive, including newer biologics, but fairly well to secretagogues such as pilocarpine. 5) No pathogenic antibodies or target epitopes have been identified to date to unify the pathogenesis of the syndrome.
All exocrine glands are innervated by the autonomic nervous system (ANS) and dysautonomia can mimic the phenotype of SjS, particularly cardinal manifestations, such as xerostomia and xerophthalmia. Thus we hypothesize that ANS dysfunction is central to the pathogenesis of SjS and propose to systematically study the ANS function in our cohort of patients with primary SjS compared with normative data from age and sex-matched controls. This protocol calls for a comprehensive evaluation of autonomic function, using physiological, neuropharmacologic, neurochemical, and imaging approaches, to identify consistent distinctive patterns of ANS involvement in SjS and thereby improve the diagnosis and understanding of pathophysiologic mechanisms of SjS.
Study design
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
Key exclusion criteria (18 listed)
- Current use of medications known to significantly influence the activity of the sympathetic or parasympathetic nervous system if they cannot be held safely at the time of ANS testing
- Known co-existing diagnosis of ANS dysfunction (for healthy volunteers)
- Medications-requiring diabetes mellitus
- Diabetic autonomic neuropathy
- Vitamin B12, folate deficiency, requiring replacement
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jul 2018.
- Background: PubMed 985434Sharma RV, Mathur SN, Ganguly J. Studies on the relative biopotencies and intestinal absorption of different apo-beta-carotenoids in rats and chickens. Biochem J. 1976 Aug 15;158(2):377-83. doi: 10.1042/bj1580377.
- Background: PubMed 14561795Arbuckle MR, McClain MT, Rubertone MV, Scofield RH, Dennis GJ, James JA, Harley JB. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med. 2003 Oct 16;349(16):1526-33. doi: 10.1056/NEJMoa021933.
- Background: PubMed 2417723Bjorklund H, Dalsgaard CJ, Jonsson CE, Hermansson A. Sensory and autonomic innervation of non-hairy and hairy human skin. An immunohistochemical study. Cell Tissue Res. 1986;243(1):51-7. doi: 10.1007/BF00221851.
- Derived from this study: PubMed 25622919Imrich R, Alevizos I, Bebris L, Goldstein DS, Holmes CS, Illei GG, Nikolov NP. Predominant Glandular Cholinergic Dysautonomia in Patients With Primary Sjogren's Syndrome. Arthritis Rheumatol. 2015 May;67(5):1345-52. doi: 10.1002/art.39044.
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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.
Stamatina J Danielides, M.D. principal investigator
National Institute of Dental and Craniofacial Research (NIDCR)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Sjogren's Syndrome and Dysautonomia, run by National Institute of Dental and Craniofacial Research (NIDCR) 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 3 inclusion and 18 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: finished, as of the sponsor's last update on 5 Jul 2018. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00565526, which also lists 4 linked publications.
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 5 Jul 2018.