DiabetesAPPATANCT05209061
Mapping the Human Appendix Using Single Cell Sequencing
An observational study of Diabetes and Appendicitis, run by Bispebjerg Hospital at 1 site in Denmark.
Trial summary
The overall purpose of this study is to describe the cellular composition of the human appendix and its gene expression using scRNAseq and scATACseq methods. This will potentially provide is with a complete and detailed map of the appendix´ immunological properties and its role in neuro-endocrine/metabolic functions. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetes, Appendicitis, Inflammatory Bowel Diseases
- What is being tested?
- Biopsy
- How many people
- 5 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Feb 2023to 10 Jun 2026
- How long will I take part?
- 1 Month
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with verified colorectal-cancer, who have been scheduled for right colectomy or ileo-ceacal resection.
Who may be able to join
- Patients undergoing a right or extended right-hemicolectomy for colon cancer
- Patients able to read and understand danish
- Patients able to give informed consent
- Patients of Scandinavian ethnicity
Who cannot join
- Previous large bowel resections
- Suspicion pre or intraoperatively of disease in the appendix
- Tumour <10cm from the appendiceal orifice.
- Known inflammatory bowel disease
- Immuno-modulation treatment
- Neo-adjuvant chemotherapy.
- < 18 years of age
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Cellular Composition of the Human Appendix Using Single-cell RNA and Single-cell ATAC-sequencing.
The overall purpose of this study is to describe the cellular composition of the human appendix and its gene expression using scRNAseq and scATACseq methods. This will potentially provide is with a complete and detailed map of the appendix´ immunological properties and its role in neuro-endocrine/metabolic functions. Our results will be held up against current knowledge of the appendix and its role in the human body and thus hopefully expand our understanding of this organ and the consequences of its removal by appendectomy.
Read the detailed description
Until recently the human appendix was viewed as a rudimentary organ without any specific function in the human body. Our current knowledge of the cellular composition of the appendix is solely based on histological examinations combined with immunohistochemical stains. These examinations have shown that the structural composition of the appendix is similar to the large intestine, with mucosa, submucosa, muscularis externa and serosa. Uniquely, the appendix has almost circumferential lymphoid follicles in the submucosa and lamina propria, and thus becomes a secondary lymphoid organ. In addition to this, the appendix contains Lieberkühn's crypts, which in contrast to the large intestine contains Paneth cells and argentaffine (enterochromaffin) neuro-endocrine cells1 2
Recently, the appendix´ role in regulation of immunologic functions has been discovered. It is believed that the great bacterial diversity in the appendix stimulates the human immune system and aids in the maturation and diversification of white blood cells, especially B-cells in the lymphoid follicles in the appendix.3 The appendix contains a larger quantity of CD5+ (B1), CD19+, Immunoglobulin-secreting IgG and secretory IgA cells compared to the large intestine. In the luminal follicle-associated epithelium, a high concentration of intra-epithelial M-cells as well as human leukocyte antigen D-related (HLA-DR) T and B cells are seen.4
The human appendix has a unique cellular composition, which plays a role in bacterial homeostasis in the large intestine5 and entero-endocrine regulation6. Furthermore, removing the appendix can drastically change incidence of certain metabolic and immune-related diseases such as type II diabetes7 and ulcerative colitis8. Despite this, only very few studies have investigated the cellular composition of the human appendix, and none of these have used single-cell (sc) RNA or DNA-sequencing to aid in our understanding of this organ.
By using scRNAseq and scATACseq (Single-cell Assay of Transposase Accessible Chromatin sequencing) we will be able to map open regions in the cell's DNA and RNA, thus providing us with a unique "map" of the cells in the appendix as well is their gene expression9-11. ScATACseq visualizes open regions in the chromatin, generating "peaks" which can then be used to map DNA motifs, such as transcription factor binding sites. With the emergence of scATACseq, chromatin accessibility is in combination with gene expression data an extremely useful resource to study cell type specific regulatory DNA interactions. To further study the immunological aspects of the appendix, we will extract immune cells from the Peyer´s plaques. Lastly, full blood will be extracted to better analyse metabolic risk factors in relation to the appendix´ metabolic cellular regulation.
- Conditions
- Diabetes, Appendicitis, Inflammatory Bowel Diseases
- Being tested
- Biopsy
- Medical subject headings
- Diabetes Mellitus, Appendicitis, Inflammatory Bowel Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BiopsyOther
Participants included in the study, will have a full thickness biopsy of the middle of the appendix taken, after the resected bowel has been removed during surgery.
| Study group | Role | What they receive |
|---|---|---|
| Colo-rectal cancer patients | Patients receiving right colectomy or ileo-ceacal resection for colorectal cancer Receives: Other: Biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Profiling of open chromatin regions
Mapping of cell types, including rare cell types, using profiling of open chromatin regions. (ATAC-seq) in biopsies from the appendix
Measured: 2 years
Evaluation of metabolic profile
Using bioimpedance, insulin and glucose measurements and CHiP-seq we will determine patient phenotype and epigenetics to evaluate their metabolic risk-profile and correlate this to cell types in the appendix
Measured: 2 years
Secondary outcomes (1)
Appendix biofilm
By sequencing bacterial DNA in our samples, we will evaluate the mucosa-associated microbiome of the appendix. This will be correlated to the two primary outcome measure
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2022
- Study start1 Feb 2023
- Primary completion28 Jan 2026
- Study completion10 Jun 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for DiabetesStudies 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
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 5 participants (actual)
- Target duration
- 1 Month
Sponsor and investigators
- Lead sponsor
- Bispebjerg Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- The Novo Nordisk Foundation Center for Basic Metabolic Research
- Responsible party
- Principal investigator, Jacob Antonsen, Bispebjerg Hospital
- Investigators
- Jacob Antonsen, MD, Principal investigator, Bispebjerg Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05209061
- Sponsor's protocol ID
- APPKOA1
- Acronym
- APPATA
- Status last verified
- Jun 2026
- First submitted
- 12 Jan 2022
- Last updated
- 12 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Data in this study is based on biological samples and data from patient registry. These data are protected by the Danish Act on Processing of Personal Data and can be accessed through application to and approval from the Danish Data Protection Agency and the Danish Health Data Authority \[https://sundhedsda tastyrelsen.dk/da/forskerservice/ansog-om-data\] where the purpose and the feasibility of the intended analysis should be accounted for.
Publications
Kooij IA, Sahami S, Meijer SL, Buskens CJ, Te Velde AA. The immunology of the vermiform appendix: a review of the literature. Clin Exp Immunol. 2016 Oct;186(1):1-9. doi: 10.1111/cei.12821. Epub 2016 Jul 19.
PubMed 27271818Somekh E, Serour F, Gorenstein A, Vohl M, Lehman D. Phenotypic pattern of B cells in the appendix: reduced intensity of CD19 expression. Immunobiology. 2000 Jan;201(3-4):461-9. doi: 10.1016/S0171-2985(00)80098-4.
PubMed 10776800Spencer J, Finn T, Isaacson PG. Gut associated lymphoid tissue: a morphological and immunocytochemical study of the human appendix. Gut. 1985 Jul;26(7):672-9. doi: 10.1136/gut.26.7.672.
PubMed 3874811Wei PL, Tsai MC, Hung SH, Lee HC, Lin HC, Lee CZ. Risk of new-onset type II diabetes after appendicectomy. Br J Surg. 2015 Sep;102(10):1267-71. doi: 10.1002/bjs.9875. Epub 2015 Jun 29.
PubMed 26122401Sahami S, Wildenberg ME, Koens L, Doherty G, Martin S, D'Haens GRAM, Cullen G, Bemelman WA, Winter D, Buskens CJ. Appendectomy for Therapy-Refractory Ulcerative Colitis Results in Pathological Improvement of Colonic Inflammation: Short-Term Results of the PASSION Study. J Crohns Colitis. 2019 Feb 1;13(2):165-171. doi: 10.1093/ecco-jcc/jjy127.
PubMed 30285094Buenrostro JD, Wu B, Chang HY, Greenleaf WJ. ATAC-seq: A Method for Assaying Chromatin Accessibility Genome-Wide. Curr Protoc Mol Biol. 2015 Jan 5;109:21.29.1-21.29.9. doi: 10.1002/0471142727.mb2129s109.
PubMed 25559105Lake BB, Codeluppi S, Yung YC, Gao D, Chun J, Kharchenko PV, Linnarsson S, Zhang K. A comparative strategy for single-nucleus and single-cell transcriptomes confirms accuracy in predicted cell-type expression from nuclear RNA. Sci Rep. 2017 Jul 20;7(1):6031. doi: 10.1038/s41598-017-04426-w.
PubMed 28729663Wagner A, Regev A, Yosef N. Revealing the vectors of cellular identity with single-cell genomics. Nat Biotechnol. 2016 Nov 8;34(11):1145-1160. doi: 10.1038/nbt.3711.
PubMed 27824854
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cellular Composition of the Human Appendix Using Single-cell RNA and Single-cell ATAC-sequencing.
- ClinicalTrials.gov ID
- NCT05209061
- Acronym / sponsor ID
- APPATA / APPKOA1
- Conditions
- Diabetes, Appendicitis, Inflammatory Bowel Diseases
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Bispebjerg HospitalUniversity, hospital or other
- Collaborators
- The Novo Nordisk Foundation Center for Basic Metabolic Research
- Study start
- 1 Feb 2023 (actual)
- Primary completion
- 28 Jan 2026 (actual)
- Study completion
- 10 Jun 2026 (actual)
- First posted
- 26 Jan 2022 (actual)
- 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.
The overall purpose of this study is to describe the cellular composition of the human appendix and its gene expression using scRNAseq and scATACseq methods. This will potentially provide is with a complete and detailed map of the appendix´ immunological properties and its role in neuro-endocrine/metabolic functions. Our results will be held up against current knowledge of the appendix and its role in the human body and thus hopefully expand our understanding of this organ and the consequences of its removal by appendectomy.
Detailed description
Until recently the human appendix was viewed as a rudimentary organ without any specific function in the human body. Our current knowledge of the cellular composition of the appendix is solely based on histological examinations combined with immunohistochemical stains. These examinations have shown that the structural composition of the appendix is similar to the large intestine, with mucosa, submucosa, muscularis externa and serosa. Uniquely, the appendix has almost circumferential lymphoid follicles in the submucosa and lamina propria, and thus becomes a secondary lymphoid organ. In addition to this, the appendix contains Lieberkühn's crypts, which in contrast to the large intestine contains Paneth cells and argentaffine (enterochromaffin) neuro-endocrine cells1 2
Recently, the appendix´ role in regulation of immunologic functions has been discovered. It is believed that the great bacterial diversity in the appendix stimulates the human immune system and aids in the maturation and diversification of white blood cells, especially B-cells in the lymphoid follicles in the appendix.3 The appendix contains a larger quantity of CD5+ (B1), CD19+, Immunoglobulin-secreting IgG and secretory IgA cells compared to the large intestine. In the luminal follicle-associated epithelium, a high concentration of intra-epithelial M-cells as well as human leukocyte antigen D-related (HLA-DR) T and B cells are seen.4
The human appendix has a unique cellular composition, which plays a role in bacterial homeostasis in the large intestine5 and entero-endocrine regulation6. Furthermore, removing the appendix can drastically change incidence of certain metabolic and immune-related diseases such as type II diabetes7 and ulcerative colitis8. Despite this, only very few studies have investigated the cellular composition of the human appendix, and none of these have used single-cell (sc) RNA or DNA-sequencing to aid in our understanding of this organ.
By using scRNAseq and scATACseq (Single-cell Assay of Transposase Accessible Chromatin sequencing) we will be able to map open regions in the cell's DNA and RNA, thus providing us with a unique "map" of the cells in the appendix as well is their gene expression9-11. ScATACseq visualizes open regions in the chromatin, generating "peaks" which can then be used to map DNA motifs, such as transcription factor binding sites. With the emergence of scATACseq, chromatin accessibility is in combination with gene expression data an extremely useful resource to study cell type specific regulatory DNA interactions. To further study the immunological aspects of the appendix, we will extract immune cells from the Peyer´s plaques. Lastly, full blood will be extracted to better analyse metabolic risk factors in relation to the appendix´ metabolic cellular regulation.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 1 Month
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Colo-rectal cancer patients | – | Other: BiopsyPatients receiving right colectomy or ileo-ceacal resection for colorectal cancer |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with verified colorectal-cancer, who have been scheduled for right colectomy or ileo-ceacal resection.
Key inclusion criteria (4 listed)
- Patients undergoing a right or extended right-hemicolectomy for colon cancer
- Patients able to read and understand danish
- Patients able to give informed consent
- Patients of Scandinavian ethnicity
Key exclusion criteria (7 listed)
- Previous large bowel resections
- Suspicion pre or intraoperatively of disease in the appendix
- Tumour <10cm from the appendiceal orifice.
- Known inflammatory bowel disease
- Immuno-modulation treatment
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 |
|---|---|---|
| BiopsyParticipants included in the study, will have a full thickness biopsy of the middle of the appendix taken, after the resected bowel has been removed during surgery. | Other | Colo-rectal cancer patients |
Primary outcome
Profiling of open chromatin regions
Time frame: 2 years
Mapping of cell types, including rare cell types, using profiling of open chromatin regions. (ATAC-seq) in biopsies from the appendix
Evaluation of metabolic profile
Time frame: 2 years
Using bioimpedance, insulin and glucose measurements and CHiP-seq we will determine patient phenotype and epigenetics to evaluate their metabolic risk-profile and correlate this to cell types in the appendix
1 secondary outcome
Appendix biofilm
Time frame: 2 years
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 12 Jun 2026.
- Background: PubMed 27271818Kooij IA, Sahami S, Meijer SL, Buskens CJ, Te Velde AA. The immunology of the vermiform appendix: a review of the literature. Clin Exp Immunol. 2016 Oct;186(1):1-9. doi: 10.1111/cei.12821. Epub 2016 Jul 19.
- Background: PubMed 10776800Somekh E, Serour F, Gorenstein A, Vohl M, Lehman D. Phenotypic pattern of B cells in the appendix: reduced intensity of CD19 expression. Immunobiology. 2000 Jan;201(3-4):461-9. doi: 10.1016/S0171-2985(00)80098-4.
- Background: PubMed 3874811Spencer J, Finn T, Isaacson PG. Gut associated lymphoid tissue: a morphological and immunocytochemical study of the human appendix. Gut. 1985 Jul;26(7):672-9. doi: 10.1136/gut.26.7.672.
- Background: PubMed 26122401Wei PL, Tsai MC, Hung SH, Lee HC, Lin HC, Lee CZ. Risk of new-onset type II diabetes after appendicectomy. Br J Surg. 2015 Sep;102(10):1267-71. doi: 10.1002/bjs.9875. Epub 2015 Jun 29.
- Background: PubMed 30285094Sahami S, Wildenberg ME, Koens L, Doherty G, Martin S, D'Haens GRAM, Cullen G, Bemelman WA, Winter D, Buskens CJ. Appendectomy for Therapy-Refractory Ulcerative Colitis Results in Pathological Improvement of Colonic Inflammation: Short-Term Results of the PASSION Study. J Crohns Colitis. 2019 Feb 1;13(2):165-171. doi: 10.1093/ecco-jcc/jjy127.
- Background: PubMed 25559105Buenrostro JD, Wu B, Chang HY, Greenleaf WJ. ATAC-seq: A Method for Assaying Chromatin Accessibility Genome-Wide. Curr Protoc Mol Biol. 2015 Jan 5;109:21.29.1-21.29.9. doi: 10.1002/0471142727.mb2129s109.
- Background: PubMed 28729663Lake BB, Codeluppi S, Yung YC, Gao D, Chun J, Kharchenko PV, Linnarsson S, Zhang K. A comparative strategy for single-nucleus and single-cell transcriptomes confirms accuracy in predicted cell-type expression from nuclear RNA. Sci Rep. 2017 Jul 20;7(1):6031. doi: 10.1038/s41598-017-04426-w.
- Background: PubMed 27824854Wagner A, Regev A, Yosef N. Revealing the vectors of cellular identity with single-cell genomics. Nat Biotechnol. 2016 Nov 8;34(11):1145-1160. doi: 10.1038/nbt.3711.
- Individual participant dataSharing planned: No. Data in this study is based on biological samples and data from patient registry. These data are protected by the Danish Act on Processing of Personal Data and can be accessed through application to and approval from the Danish Data Protection Agency and the Danish Health Data Authority [https://sundhedsda tastyrelsen.dk/da/forskerservice/ansog-om-data] where the purpose and the feasibility of the intended analysis should be accounted for.
Related trials for Diabetes
Recruiting
Clinical Study to Evaluate the Impact of the Accu-Chek SmartGuide CGM Solution on the Mean Change in Time in Range Compared With Self-Monitoring of Blood Glucose in Participants With Type 1 and Type 2 Diabetes Mellitus
Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus
Not yet recruitingPhase 2
Effects of Meal Macronutrients on Postprandial Lipids
Nephrotic Syndrome, Lipodystrophy
Enrolling by invitation
MTM2MTG Pilot Ancillary Study
Diet, Healthy, HbA1c
Active, not recruitingPhase 3
Compassionate Use of Metreleptin in Previously Treated People With Generalized Lipodystrophy
Lipodystrophy, Diabetes
Active, not recruitingPhase 2
Islet Cell Transplant for Type 1 Diabetes
Type 1 Diabetes Mellitus
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.
Jacob Antonsen, MD principal investigator
Bispebjerg Hospital
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 Diabetes and Appendicitis, run by Bispebjerg Hospital at 1 site in Denmark.
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 4 inclusion and 7 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 12 Jun 2026. 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 Denmark. 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?
Profiling of open chromatin regions (time frame: 2 years). The study lists 2 primary outcomes in all. 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 NCT05209061, which also lists 8 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 12 Jun 2026.