Sjogren's SyndromePhase 4NCT00543166
Sex Steroids in Sjögren's Syndrome: Effect of Substitution Treatment on Fatigue
A Phase 4 study testing dehydroepiandrosterone in people with Sjogren's Syndrome, run by University of Helsinki at 1 site in Finland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Sjogren's Syndrome
- What is being tested?
- dehydroepiandrosterone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 107 participants
- Where
- 1 siteFinland
- Study dates
- Feb 2003to Dec 2009
- Phase
- Phase 4
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Primary SS according to the American-European consensus criteria
- 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)
- subnormal serum S-DHEAS values (the reference values were calculated based on a pilot study of 81 healthy women and 57 healthy men).
Who cannot join
- Age <18 years or >80 years
- prisoner
- individuals not able to give their informed consent
- history of breast cancer
- history of uterus cancer
- history of prostatic cancer
Show all 12Show fewer
- history of stroke or prothrombotic coagulation disorders
- pregnant or lactating women
- fertile patients without adequate prevention
- difficult acne
- a significant liver disease
- 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
Trial locations and contacts
1 site in 1 country.
Finland1 site
Department of Medicine, Helsinki University Central Hospital
Helsinki, Helsinki, 00029
About this study
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.
Read the 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.
- Conditions
- Sjogren's Syndrome
- Being tested
- dehydroepiandrosterone
- Keywords
- Sjögren's syndrome, fatigue, salivary gland, dehydroepiandrosterone
- Medical subject headings
- Sjogren's Syndrome, Fatigue
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
dehydroepiandrosteroneDrug
Also called DHEA
50 mg of dehydroepiandrosterone in the morning for 4 months in the treatment group.
| Study group | Role | What they receive |
|---|---|---|
| 2 | Placebo comparator | 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. Receives: Drug: dehydroepiandrosterone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fatigue
Measured: prospective
Secondary outcomes (1)
Quality of life
Measured: prospective
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2007 (estimated)
- Study startFeb 2003
- Study completionDec 2009 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 107 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Helsinki
- Sponsor type
- University, hospital or other
- Collaborators
- Göteborg University, Uppsala University
- Investigators
- Yrjö Konttinen, MD, PhD, Principal investigator, Helsinki University Central Hospital, Helsinki, Finland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00543166
- Sponsor's protocol ID
- T101090002
- Status last verified
- Oct 2007
- First submitted
- 9 Oct 2007
- Last updated
- 5 Nov 2007
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Laine M, Virtanen I, Salo T, Konttinen YT. Segment-specific but pathologic laminin isoform profiles in human labial salivary glands of patients with Sjogren's syndrome. Arthritis Rheum. 2004 Dec;50(12):3968-73. doi: 10.1002/art.20730.
PubMed 15593200Konttinen YT, Tensing EK, Laine M, Porola P, Tornwall J, Hukkanen M. Abnormal distribution of aquaporin-5 in salivary glands in the NOD mouse model for Sjogren's syndrome. J Rheumatol. 2005 Jun;32(6):1071-5.
PubMed 15940770Valtysdottir ST, Wide L, Hallgren R. Low serum dehydroepiandrosterone sulfate in women with primary Sjogren's syndrome as an isolated sign of impaired HPA axis function. J Rheumatol. 2001 Jun;28(6):1259-65.
PubMed 11409117Laine M, Porola P, Udby L, Kjeldsen L, Cowland JB, Borregaard N, Hietanen J, Stahle M, Pihakari A, Konttinen YT. Low salivary dehydroepiandrosterone and androgen-regulated cysteine-rich secretory protein 3 levels in Sjogren's syndrome. Arthritis Rheum. 2007 Aug;56(8):2575-84. doi: 10.1002/art.22828.
PubMed 17665393Virkki LM, Porola P, Forsblad-d'Elia H, Valtysdottir S, Solovieva SA, Konttinen YT. Dehydroepiandrosterone (DHEA) substitution treatment for severe fatigue in DHEA-deficient patients with primary Sjogren's syndrome. Arthritis Care Res (Hoboken). 2010 Jan 15;62(1):118-24. doi: 10.1002/acr.20022.
PubMed 20191499
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2007. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sex Steroids in Sjögren's Syndrome: Effect of Substitution Treatment on Fatigue
- ClinicalTrials.gov ID
- NCT00543166
- Acronym / sponsor ID
- T101090002
- Conditions
- Sjogren's Syndrome
- Keywords
- Sjögren's syndrome, fatigue, salivary gland, dehydroepiandrosterone
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 107 participants (actual)
- Lead sponsor
- University of HelsinkiUniversity, hospital or other
- Collaborators
- Göteborg University, Uppsala University
- Study start
- Feb 2003
- Study completion
- Dec 2009 (estimated)
- First posted
- 12 Oct 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.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 2 | Placebo comparator | Drug: dehydroepiandrosterone180 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Primary SS according to the American-European consensus criteria
- 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)
- subnormal serum S-DHEAS values (the reference values were calculated based on a pilot study of 81 healthy women and 57 healthy men).
Key exclusion criteria (12 listed)
- Age <18 years or >80 years
- prisoner
- individuals not able to give their informed consent
- history of breast cancer
- history of uterus cancer
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 |
|---|---|---|
| dehydroepiandrosteroneAlso: DHEA50 mg of dehydroepiandrosterone in the morning for 4 months in the treatment group. | Drug | 2 |
Primary outcome
Fatigue
Time frame: prospective
1 secondary outcome
Quality of life
Time frame: prospective
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2007.
- Background: PubMed 15593200Laine M, Virtanen I, Salo T, Konttinen YT. Segment-specific but pathologic laminin isoform profiles in human labial salivary glands of patients with Sjogren's syndrome. Arthritis Rheum. 2004 Dec;50(12):3968-73. doi: 10.1002/art.20730.
- Background: PubMed 15940770Konttinen YT, Tensing EK, Laine M, Porola P, Tornwall J, Hukkanen M. Abnormal distribution of aquaporin-5 in salivary glands in the NOD mouse model for Sjogren's syndrome. J Rheumatol. 2005 Jun;32(6):1071-5.
- Background: PubMed 11409117Valtysdottir ST, Wide L, Hallgren R. Low serum dehydroepiandrosterone sulfate in women with primary Sjogren's syndrome as an isolated sign of impaired HPA axis function. J Rheumatol. 2001 Jun;28(6):1259-65.
- Results publication: PubMed 17665393Laine M, Porola P, Udby L, Kjeldsen L, Cowland JB, Borregaard N, Hietanen J, Stahle M, Pihakari A, Konttinen YT. Low salivary dehydroepiandrosterone and androgen-regulated cysteine-rich secretory protein 3 levels in Sjogren's syndrome. Arthritis Rheum. 2007 Aug;56(8):2575-84. doi: 10.1002/art.22828.
- Derived from this study: PubMed 20191499Virkki LM, Porola P, Forsblad-d'Elia H, Valtysdottir S, Solovieva SA, Konttinen YT. Dehydroepiandrosterone (DHEA) substitution treatment for severe fatigue in DHEA-deficient patients with primary Sjogren's syndrome. Arthritis Care Res (Hoboken). 2010 Jan 15;62(1):118-24. doi: 10.1002/acr.20022.
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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.
Yrjö Konttinen, MD, PhD principal investigator
Helsinki University Central Hospital, Helsinki, Finland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing dehydroepiandrosterone in people with Sjogren's Syndrome, run by University of Helsinki at 1 site in Finland.
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 12 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: status not confirmed, as of the sponsor's last update on 5 Nov 2007. 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 Finland. 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. Some participants in this study may receive a placebo. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
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?
Fatigue (time frame: prospective). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00543166, which also lists 5 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 Nov 2007.