ImmunotoxicityBIS-MANCT02794896
Anesthetic Depth Effects Upon Immune Competent Cells
A study testing High dose propofol, fentanyl and sevoflurane and Low dose propofol, fentanyl and sevoflurane in people with Immunotoxicity and Anesthesia, run by Heidelberg University at 1 site in Germany.
Trial summary
Anesthesia depth affects the proliferation of lymphocytes to NK-cells and memory T-cells effect and the phagocytosis activity of macrophages in healthy patients. ASA 1-3 subjects undergoing extended shoulder surgery under continuous regional anesthesia randomly were assigned to a deep or a shallow anesthesia level… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Immunotoxicity, Anesthesia, Inert Gas Narcosis
- What is being tested?
- High dose propofol, fentanyl and sevoflurane and Low dose propofol, fentanyl and sevoflurane
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteGermany
- Study dates
- Mar 2009to Mar 2013
- Phase
- Interventional
- 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
- enrolment for longer shoulder surgery
- consent for the standard anesthesia form in combination with the interscalene plexus block
- ASA Status 1-3
Who cannot join
- sedative premedication
- severe immune deficiency (diabetes, steroid or antihistamine medication, cancer, chemotherapy,
- status post transplantation, drug and alcohol abuse),
- recent surgery (1 month) or blood transfusion
Trial locations and contacts
1 site in 1 country.
Germany1 site
University Medicine of Mannheim, Dept. Anesthesiology and Critical Care Medicine
Mannheim, 68163
About this study
Official title: Hypnotic Depth Reduces Lymphocyte Proliferation to Natural Killer Cells, B-cells, Memory T-cells, Depresses Intracellular Oxidative Burst and Changes Protein Expression Pattern of Monocytes
Anesthesia depth affects the proliferation of lymphocytes to NK-cells and memory T-cells effect and the phagocytosis activity of macrophages in healthy patients. ASA 1-3 subjects undergoing extended shoulder surgery under continuous regional anesthesia randomly were assigned to a deep or a shallow anesthesia level (BIS <35 or >55) for more than an hour. Immune response is measured by lymphocyte proliferation as well as neutrophil and monocyte phagocytosis activity.
Read the detailed description
Blood samples were taken under minimal stress prior to anesthesia induction (T0), recovery (T1) and 12 weeks following hospital discharge (T2) from the respective anesthesia depth level. Bispectral index monitoring (BIS) was performed from the awake state to complete recovery in all subjects.
Hemoglobin concentration, leukocyte and lymphocyte counts were determined by routine automated laboratory techniques. Lymphocyte proliferation was analyzed by SASPA flow cytometry analysis. In brief, 100 µl EDTA blood were stirred with 10 µl FITC and PE marked antibody mixture containing CD3, CD4, CD8, CD 16, CD45, CD28, CD27, CD 56.
Monocyte and neutrophil phagocytosis activity was measured separately in macrophages of fresh heparinized whole blood using flow cytometric test kits.
Proteomics of monocytes was done synchronously.
- Conditions
- Immunotoxicity, Anesthesia, Inert Gas Narcosis
- Being tested
- High dose propofol, fentanyl and sevoflurane, Low dose propofol, fentanyl and sevoflurane
- Medical subject headings
- Inert Gas Narcosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High dose propofol, fentanyl and sevofluraneDrug
Also called BIS lower than or equal to 45
Deep Anesthesia
Low dose propofol, fentanyl and sevofluraneDrug
Also called BIS above 45
Shallow Anesthesia
| Study group | Role | What they receive |
|---|---|---|
| Deep Anesthesia | Experimental | Standard anesthesia with fentanyl, propofol for shoulder surgery together with a interscalene plexus block was performed. The anesthesiologist only was informed about the group allocation by the study director and tried to control best for maintenance on target anesthesia level BIS 45 (group 1, deep anesthesia). Anesthesia depth was measured by BIS monitors (BIS Vista, Aspect) for every minute and the minutes below or equal to a BIS level of 45 were counted. Receives: Drug: High dose propofol, fentanyl and sevoflurane |
| Shallow Anesthesia | Experimental | Standard anesthesia with fentanyl, propofol for shoulder surgery together with a inter scalene plexus block was performed. The anesthesiologist only was informed about the group allocation by the study director and tried to control best for maintenance on target anesthesia level BIS ≥ 55 (group 2, shallow anesthesia). Anesthesia depth as measured by BIS monitors (BIS Vista, Aspect) for every minute and the minutes above a BIS level of 45 were counted. Receives: Drug: Low dose propofol, fentanyl and sevoflurane |
What is being measured
The primary outcome is the main question the study is designed to answer.
Depression of lymphocyte proliferation by CD expression pattern in SASPA-Test as given in a percentage from before anesthesia
before and following anesthesia period over 60 min
Measured: 70-90 min
Secondary outcomes (2)
Reduction of phagocytosis activity as a percentage of base line (prior to anesthesia)
before and following anesthesia period over 60 min
Measured: 70-90 min
Protein expression pattern of monocytes by proteomics analysis and mass spectrometry
before and following anesthesia period over 60 min
Measured: 70-90 min
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2016 (estimated)
- Study startMar 2009
- Primary completionMar 2012
- Study completionMar 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ImmunotoxicityStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Heidelberg University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Thomas Frietsch, Universitätsmedizin Mannheim
- Investigators
- Thomas Frietsch, MD, PhD, Principal investigator, University of Mannheim
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02794896
- Sponsor's protocol ID
- Anesthetic depth-MA
- Acronym
- BIS-MA
- Status last verified
- May 2022
- First submitted
- 12 May 2016
- Last updated
- 24 May 2022
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: per request
Publications
Nguyen XD, Horn A, Fischer D, Beck G, Spannenberger CC, Gaudilliere B, Horn JL, Thierse HJ, Frietsch T. Suppressive effects of deep balanced anesthesia on cellular immunity and protein expression: a randomized-controlled pilot study. BMC Anesthesiol. 2025 Mar 17;25(1):129. doi: 10.1186/s12871-025-02980-9.
PubMed 40097954
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hypnotic Depth Reduces Lymphocyte Proliferation to Natural Killer Cells, B-cells, Memory T-cells, Depresses Intracellular Oxidative Burst and Changes Protein Expression Pattern of Monocytes
- ClinicalTrials.gov ID
- NCT02794896
- Acronym / sponsor ID
- BIS-MA / Anesthetic depth-MA
- Conditions
- Immunotoxicity, Anesthesia, Inert Gas Narcosis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Heidelberg UniversityUniversity, hospital or other
- Study start
- Mar 2009
- Primary completion
- Mar 2012 (actual)
- Study completion
- Mar 2013 (actual)
- First posted
- 9 Jun 2016 (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.
Anesthesia depth affects the proliferation of lymphocytes to NK-cells and memory T-cells effect and the phagocytosis activity of macrophages in healthy patients. ASA 1-3 subjects undergoing extended shoulder surgery under continuous regional anesthesia randomly were assigned to a deep or a shallow anesthesia level (BIS <35 or >55) for more than an hour. Immune response is measured by lymphocyte proliferation as well as neutrophil and monocyte phagocytosis activity.
Detailed description
Blood samples were taken under minimal stress prior to anesthesia induction (T0), recovery (T1) and 12 weeks following hospital discharge (T2) from the respective anesthesia depth level. Bispectral index monitoring (BIS) was performed from the awake state to complete recovery in all subjects.
Hemoglobin concentration, leukocyte and lymphocyte counts were determined by routine automated laboratory techniques. Lymphocyte proliferation was analyzed by SASPA flow cytometry analysis. In brief, 100 µl EDTA blood were stirred with 10 µl FITC and PE marked antibody mixture containing CD3, CD4, CD8, CD 16, CD45, CD28, CD27, CD 56.
Monocyte and neutrophil phagocytosis activity was measured separately in macrophages of fresh heparinized whole blood using flow cytometric test kits.
Proteomics of monocytes was done synchronously.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Deep Anesthesia | Experimental | Drug: High dose propofol, fentanyl and sevofluraneStandard anesthesia with fentanyl, propofol for shoulder surgery together with a interscalene plexus block was performed. The anesthesiologist only was informed about the group allocation by the study director and tried to control best for maintenance on target anesthesia level BIS 45 (group 1, deep anesthesia). Anesthesia depth was measured by BIS monitors (BIS Vista, Aspect) for every minute and the minutes below or equal to a BIS level of 45 were counted. |
| Shallow Anesthesia | Experimental | Drug: Low dose propofol, fentanyl and sevofluraneStandard anesthesia with fentanyl, propofol for shoulder surgery together with a inter scalene plexus block was performed. The anesthesiologist only was informed about the group allocation by the study director and tried to control best for maintenance on target anesthesia level BIS ≥ 55 (group 2, shallow anesthesia). Anesthesia depth as measured by BIS monitors (BIS Vista, Aspect) for every minute and the minutes above a BIS level of 45 were counted. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- enrolment for longer shoulder surgery
- consent for the standard anesthesia form in combination with the interscalene plexus block
- ASA Status 1-3
Key exclusion criteria (4 listed)
- sedative premedication
- severe immune deficiency (diabetes, steroid or antihistamine medication, cancer, chemotherapy,
- status post transplantation, drug and alcohol abuse),
- recent surgery (1 month) or blood transfusion
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 |
|---|---|---|
| High dose propofol, fentanyl and sevofluraneAlso: BIS lower than or equal to 45Deep Anesthesia | Drug | Deep Anesthesia |
| Low dose propofol, fentanyl and sevofluraneAlso: BIS above 45Shallow Anesthesia | Drug | Shallow Anesthesia |
Primary outcome
Depression of lymphocyte proliferation by CD expression pattern in SASPA-Test as given in a percentage from before anesthesia
Time frame: 70-90 min
before and following anesthesia period over 60 min
2 secondary outcomes
Reduction of phagocytosis activity as a percentage of base line (prior to anesthesia)
Time frame: 70-90 min
Protein expression pattern of monocytes by proteomics analysis and mass spectrometry
Time frame: 70-90 min
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 24 May 2022.
- Derived from this study: PubMed 40097954Nguyen XD, Horn A, Fischer D, Beck G, Spannenberger CC, Gaudilliere B, Horn JL, Thierse HJ, Frietsch T. Suppressive effects of deep balanced anesthesia on cellular immunity and protein expression: a randomized-controlled pilot study. BMC Anesthesiol. 2025 Mar 17;25(1):129. doi: 10.1186/s12871-025-02980-9.
- Individual participant dataSharing planned: Yes. per request
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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.
Thomas Frietsch, MD, PhD principal investigator
University of Mannheim
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing High dose propofol, fentanyl and sevoflurane and Low dose propofol, fentanyl and sevoflurane in people with Immunotoxicity and Anesthesia, run by Heidelberg University at 1 site in Germany.
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 4 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 24 May 2022. 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 Germany. 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.
What does the primary outcome measure?
Depression of lymphocyte proliferation by CD expression pattern in SASPA-Test as given in a percentage from before anesthesia (time frame: 70-90 min). 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 NCT02794896, which also lists 1 linked publication.
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 24 May 2022.