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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00543166
Recruitment Status : Unknown
Verified October 2007 by University of Helsinki.
Recruitment status was:  Active, not recruiting
First Posted : October 12, 2007
Last Update Posted : November 5, 2007
Göteborg University
Uppsala University
Information provided by:
University of Helsinki

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Sjogren's Syndrome Drug: dehydroepiandrosterone Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 107 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Sex Steroids in Sjögren's Syndrome: Effect of Substitution Treatment on Fatigue
Study Start Date : February 2003
Estimated Study Completion Date : December 2009

Resource links provided by the National Library of Medicine

Drug Information available for: Prasterone

Arm Intervention/treatment
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 Name: DHEA

Primary Outcome Measures :
  1. Fatigue [ Time Frame: prospective ]

Secondary Outcome Measures :
  1. Quality of life [ Time Frame: prospective ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00543166

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Department of Medicine, Helsinki University Central Hospital
Helsinki, Finland, 00029
Sponsors and Collaborators
University of Helsinki
Göteborg University
Uppsala University
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Principal Investigator: Yrjö Konttinen, MD, PhD Helsinki University Central Hospital, Helsinki, Finland

Publications of Results:
Other Publications:
Publications automatically indexed to this study by Identifier (NCT Number):
Layout table for additonal information Identifier: NCT00543166    
Other Study ID Numbers: T101090002
First Posted: October 12, 2007    Key Record Dates
Last Update Posted: November 5, 2007
Last Verified: October 2007
Keywords provided by University of Helsinki:
Sjögren's syndrome
salivary gland
Additional relevant MeSH terms:
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Sjogren's Syndrome
Pathologic Processes
Signs and Symptoms
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Salivary Gland Diseases
Mouth Diseases
Stomatognathic Diseases
Dry Eye Syndromes
Lacrimal Apparatus Diseases
Eye Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs