Sex Steroids in Sjögren's Syndrome: Effect of Substitution Treatment on Fatigue

November 2, 2007 updated by: University of Helsinki
Our research contributes to the understanding of some of the basic biology of the salivary glands. The etiology and many of the pathomechanisms of Sjögren's syndrome are unknown. In particular, reasons for the female dominance, late age of onset, fatigue and the prominent involvement of exocrine glands are unknown. We hypothesize, due to the disease characteristics, that the primary target hit by the disease process is the secretory acinar cell and that this cell is particularly damaged in women due to insufficient support, normally provided by dehydroepiandrosterone and its intracrine processing.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

We hypothesize, due to the Sjögren's syndrome (SS) disease characteristics, that the primary target hit by the disease process is the secretory acinar cell and that this cell is particularly in women damaged due to insufficient support, normally provided by dehydroepiandrosterone and its intracrine processing. Dehydroepiandrosterone deficiency at the time of adrenopause seems to us as the more likely endocrine trigger than estrogen deficiency caused by menopause as androgens in general are considered to be protective against autoimmunity and estrogens to favor it. Acinar cell is normally responsible for the production of primary saliva. Acinar cell damage can lead to acinar cell apoptosis and loss. Normally this is compensated by division of the acinar cells in situ or, according to recent reports, perhaps rather by division and subsequent migration of one of the daughter cells into the acinar space and transdifferentiation of this intercalated ductal cell progenitor into mature acinar cell. In SS this remodeling seems to be impaired, perhaps for the same reason, which also leads to primary acinar cell damage. According to this hypothesis, the primary changes occur in the salivary glands and more specifically in the acinar cells, whereas immune activation and autoimmunity are secondarily activated against abnormally damaged acinar cells so that individuals with the "right" genetic background also produce SS-A and SS-B antibodies. The cause of the acinar cell damage may not be a direct, damaging stimulus, e.g. virus infection or irradiation damage, but rather lack of a supporting anabolic stimulus and inadequate maintenance of the acinar cell health leading to cytopathic acinar cell changes. In peri-menopausal women (who still produce some estrogens) this abnormal antigen release and processing from acinar cells, which reveals cryptic epitopes, together with autoimmunity enhancing effects of estrogens, may lead to the full picture of SS (Cutolo et al., 2004).

This neuroimmunoendocrine working hypothesis would explain many central disease characteristics, but does not provide a final answer to the mystery of this intriguing syndrome as the reasons for the insufficient production and generation of DHEA remain to be solved. We have done some preliminary studies to analyze this topic by mapping the signals of the extracellular matrix in the adrenal cortex, where the cells proliferate in the outer zone and subsequently migrate in a centripetal direction, during which phenotypic transition occurs from the outer zone (zona glomerulosa) cells producing aldosterone to the intermediate zone (zona fasciculata) cells producing glucocorticosteroids and finally to the inner zone (zona reticularis) cells producing DHEA. However, in this research project we have decided to totally focus on the salivary gland acinar cell-sex steroid interactions.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
107

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Finland
      • Helsinki, Finland, 00029
        • Department of Medicine, Helsinki University Central Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Primary SS according to the American-European consensus criteria
  2. General Fatigue ≥14 calculated from MFI-20 (Multiple fatigue inventory-20 questionnaire; the value was based on a pilot study of 239 members of the Finnish SS patient association)
  3. subnormal serum S-DHEAS values (the reference values were calculated based on a pilot study of 81 healthy women and 57 healthy men).

Exclusion Criteria:

  1. Age <18 years or >80 years
  2. prisoner
  3. individuals not able to give their informed consent
  4. history of breast cancer
  5. history of uterus cancer
  6. history of prostatic cancer
  7. history of stroke or prothrombotic coagulation disorders
  8. pregnant or lactating women
  9. fertile patients without adequate prevention
  10. difficult acne
  11. a significant liver disease
  12. patients with changes in their systemic medication taken for SS during the previous three months 13) patients taking more than 10 mg prednisolone per day

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: 2
180 patients divided to two separate groups (each containing 90 patients). This study has a cross-over, wash-out design, which consists of two 4 month treatment period separated by a one month long wash-out period. During one treatment period the patient gets placebo and during one of the treatment periods the patient gets 50mg of dehydroepiandrosterone (DHEA) in the morning.
Drug: dehydroepiandrosterone
50 mg of dehydroepiandrosterone in the morning for 4 months in the treatment group.
Other Names:
  • DHEA

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Fatigue
Time Frame: prospective
prospective

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Quality of life
Time Frame: prospective
prospective

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Helsinki

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Uppsala University
Göteborg University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Yrjö Konttinen, MD, PhD, Helsinki University Central Hospital, Helsinki, Finland

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2003

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2009

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 9, 2007

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 11, 2007

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 12, 2007

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 4, 2007

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 2, 2007

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • T101090002

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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