Effects of filarial parasite infection on type 2 diabetes
| ISRCTN | ISRCTN43845142 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN43845142 |
| Secondary identifying numbers | FIMMIP HU 2144/3-1 |
- Submission date
- 27/11/2019
- Registration date
- 02/12/2019
- Last edited
- 23/01/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Infections and Infestations
Plain English summary of protocol
Background and study aims
Type 2 diabetes is a growing challenge for health care systems in Africa. In Cameroon, more than half a million patients suffer from diabetes. Diabetes is one of the major causes for global mortality, morbidity and health care expenditures, which will aggravate especially in Africa, where around 67% of diabetic subjects are undiagnosed and it is predicted that until 2035, the number of diabetes patients will more than double.
Filariasis is a parasitic disease caused by an infection with roundworms of the Filarioidea type. These are spread by blood-feeding diptera such as black flies and mosquitoes. This disease belongs to the group of diseases called helminthiases. Eight known filarial nematodes use humans as their definitive hosts.
It is important to elucidate the effect of helminth infections and their impact on diabetes. Therefore this study will investigate the impact of filarial infections on immune and metabolic profiles to predict the risk to develop diabetes.
The objectives of the study are
1. To investigate the association between human filarial infections and other diseases such as diabetes, high blood pressure etc.
2. To elucidate whether treatment against filariae affects other diseases such as diabetes, high blood pressure etc.
Who can participate?
To participate in this research, participants must be between 18 and 60 years of age and their body mass index (BMI) should be 30 or greater or alternatively below 25. We will screen for O. volvulus, M. perstans, Loa Loa and include patients that are either positive for one of those helminth infections or lack helminth infections (endemic controls). The study participants should not have clinical signs of tuberculosis, HIV, any known chronic disease.
What does the study involve?
Onchocerca volvulus, Mansonella perstans infected participants will receive 200 mg of doxycycline daily for 6 weeks, which will eliminate the filarial infection. Patients co-infected with Onchocerca and Mansonella will also be treated with 200 mg of doxycycline daily for 6 weeks. As L. loa does not contain Wolbachia endosymbionts, doxycycline treatment will not affect L. loa co-infection. In addition, onchocerciasis patients, M. perstans infected patients, and L. loa infected individuals and endemic controls will receive a single dose of 400 mg albendazole every 3 months with a total of four treatments for the elimination of soil-transmitted helminths.
Blood sample collection will occur at baseline, 12 months and 24 months. For the determination of intestinal helminths, the researchers will additionally require stool samples at baseline, follow-up, 12 months and 24 months. To determine Onchocerca volvulus infection and microfilarial density, the researchers will perform two skin snips (a superficial cut of the skin) the size of a fingertip at baseline, 12 months and 24 months.
What are the possible benefits and risks of participating?
Benefits: treatment of the infection
Risks: We do not expect any major risks, but the patient could feel some discomforts due to blood drawing.
Where is the study run from?
District de Sante de Manjo in Cameroon
When is the study starting and how long is it expected to run for?
January 2020 to December 2026
Who is funding the study?
German Research Foundation
Who is the main contact?
1. Dr Marc Hübner (scientific)
Huebner@uni-bonn.de
2. Prof. Samuel Wanji
samwandji@gmail.com
Contact information
Scientific
Institute for Medical Microbiology, Immunology and Parasitology
University Hospital of Bonn
Venusberg-Campus 1 Building 63
Bonn
53127
Germany
 ORCID ID |
0000-0001-8885-418X |
|---|---|
| Phone | +49 228-287-19177 |
| Huebner@uni-bonn.de |
Public
Department of Microbiology and Parasitology
Faculty of Science
University of Buea
Buea
P.O.Box 63
Cameroon
| ORCID ID |
0000-0003-0022-8366 |
|---|---|
| Phone | +237 694-727715 |
| samwandji@gmail.com |
Study information
| Study design | Interventional controlled open-label pilot trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Community |
| Study type | Screening |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Impact of human filarial infections on the metabolic and immunological profile in type 2 diabetes |
| Study acronym | FIMMIP |
| Study objectives | 1. Immunomodulation by infections with the filarial nematodes Mansonella perstans and Onchocerca volvulus improves the glycaemic and metabolic parameters. 2. Anti-filarial therapy has adverse effects on the metabolic and immunological profile of obese and lean filariasis patients. |
| Ethics approval(s) | 1. Approved 10/10/2017, changes approved 22/12/2021, Comite National D´ethique De La Recherche Pour La Sante Humaine (National committee on the ethics of research for human health, Medical research Station, P.O. Box 55, Kumba, Cameroon; +237 33354231; cnethique_minsante@yahoo.fr) ref: No2019/03/1153CE/CNERSH/SP 2. Approved 20/03/2018, changes approved 13/12/2021, Rheinische Friedrich-Wilhelms-Universität, Medizinische Fakultät, Ethik Kommission (Ethics commission of the faculty of medicine, Building 13, Room 2G 029, Rheinische Friedrich-Wilhelms-Universität, Venusberg-Campus 1, Biomedizinisches Zentrum, Bonn, Germany; +49-228-287-5193; ethik@uni-bonn.de), ref: 046/18 |
| Health condition(s) or problem(s) studied | Human filarial infection and type 2 diabetes |
| Intervention | Current interventions as of 24/01/2022: 1. Patients infected with M. perstans: Patients will be divided into lean (BMI <25) and obese (BMI ≥ 30). All volunteering patients will receive the interventional treatment 200 mg of doxycycline daily for 6 weeks. All volunteering patients who refuse treatment will serve as an untreated control. All participants will receive a single dose of 400 mg albendazole every 3 months with a total of four treatments for the elimination of soil-transmitted helminths. Treatment of L. loa co-infected individuals with doxycycline and albendazole does not kill the adult L. loa filariae. 2. Patients infected with O. volvulus: Patients will be divided into lean (BMI <25) and obese (BMI ≥ 30). All volunteering patients will be treated with interventional treatment 200 mg of doxycycline daily for 6 weeks. All volunteering patients who refuse treatment will serve as an untreated control. All participants will receive a single dose of 400 mg albendazole every 3 months with a total of four treatments for the elimination of soil-transmitted helminths. Treatment of L. loa co-infected individuals with doxycycline and albendazole does not kill the adult L. loa filariae. 3. Endemic Normals (not infected with M. perstans or O. volvulus or any other helminths or disease mentioned in the exclusion criteria). Participants will be divided into lean (BMI <25) and obese (BMI ≥ 30). All volunteering participants will be treated with a single dose of 400 mg albendazole every 3 months with a total of four treatments for the elimination of soil-transmitted helminths. 4. Loa loa infected Participants infected with Loa loa will receive a single dose of 400 mg albendazole every 3 months with a total of four treatments for the elimination of soil-transmitted helminths. Treatment of L. loa co-infected individuals with albendazole does not kill the adult L. loa filariae. Blood sample collection will occur at baseline, 12 months and 24 months. For the determination of intestinal helminths the researchers will additionally require stool samples at baseline, follow-up, 12 months and 24 months. To determine Onchocerca volvulus infection and microfilarial density, the researchers will perform two skin snips (a superficial cut of the skin) the size of a fingertip at baseline, 12 months and 24 months. All subjects will be followed up 12 and 24 months post-treatment and the immunological and disease-related parameters will be analyzed Previous interventions: 1. Patients infected with M. perstans: Patients will be divided into lean (BMI <25) and obese (BMI ≥ 30). From each group half of the patients will receive the interventional treatment (200 mg of doxycycline daily for 6 weeks) and the other half will be the control. (Participants of this study will obtain an individual code and the code will be referred to Bonn, Germany, where we will randomly allocate half of the participants of group 1 to doxycycline treatment, without knowing any details of the participants. The individual codes of the selected participants for doxycycline therapy will then be forwarded to our partners in Cameroon.) 2. Patients infected with O. volvulus: Patients will be divided into lean (BMI <25) and obese (BMI ≥ 30). All volunteering patients will be treated with four rounds of 150µg/kg ivermectin (Mectizan) in 3-month intervals in the process of a community-based mass drug administration (MDA). Patients who refuse treatment will serve as an untreated control. 3. Endemic Normals (not infected with M. perstans or O. volvulus or any other helminths or disease mentioned in the exclusion criteria). Patients will be divided into lean (BMI <25) and obese (BMI ≥ 30). All volunteering patients will be treated with four rounds of 150 µg/kg ivermectin (Mectizan) in 3-month intervals in the process of a community-based mass drug administration (MDA). Patients who refuse treatment will serve as an untreated control. In addition: 400 mg albendazole every 3 months with a total of four treatments for groups 1, 2 and 3. Blood sample collection will occur at baseline, 12 months and 24 months. For the determination of intestinal helminths we will additionally require 3 stool samples at baseline, 12 months and 24 months. To determine Onchocerca volvulus infection and microfilarial density, we will perform two skin snips (a superficial cut of the skin) the size of fingertip at baseline, 12 months and 24 months. All subjects will be followed up 12 and 24 months post-treatment and the immunological and disease-related parameters will be analyzed |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Doxycycline, ivermectin, albendazole |
| Primary outcome measure | Measured using blood test at baseline and follow-up (12 and 24 months): 1. Fasting glucose measured by autoanalzyer 2. HbA1C measured by Reflotron; updated 24/01/2022: HbA1C measured by HumaStar200 3. Serum insulin measured by ELISA 4. HOMA-IR measured by the homeostasis assessment (HOMA) model (fasting insulin (mIU/ml) × fasting) |
| Secondary outcome measures | Measured using blood test at baseline and follow-up (12 and 24 months): 1. Alpha-2- macroglobulin, C-peptide, TNF, IL-6, IL-10, adipokines, gut hormones, IgG subtypes, IgE, IgA (by ELISA or multiplex) 2. Total and differential cell counts (by automated differential cell counter) 3. Quantification of naïve, effector and central memory CD4+ and CD8+ T cells, regulatory T cells (Tregs), NK cells, dendritic cells (DC) and B cells in whole blood, cytokine producing T cells (by flow cytometry) 4. Lipid profile (total, HDL and LDL cholesterol, triglycerides – by autoanalyzer and Friedewald equation for LDL); AST, ALT, ALP, GGT, serum creatinine, urea, urine albumin, (by autoanalyzer) 5. Body weight, BMI, adipose tissue and muscle ratio (by weight scale body fat analyzer) 6. Blood pressure (blood pressure measurement device) 7. Waist and hip circumference (measuring tape) 8. Measured at baseline only: Questionnaire on medical history, dietary and physical behavior |
| Overall study start date | 01/08/2016 |
| Completion date | 31/12/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 60 Years |
| Sex | Both |
| Target number of participants | 400 M. perstans-infected individuals, 400 O. volvulus-infected subjects, 400 endemic normal subjects |
| Total final enrolment | 2171 |
| Key inclusion criteria | Current inclusion criteria as of 24/01/2022: 1. Willingness to participate in the study as evidenced by signing the Informed consent form 2. Participants will be male and female between 18-60 years old 3. BMI equal to or above 30 or below 25 4. Body weight >40 kg 5. Last intake of ivermectin at least 4 months ago 6. Last intake of anti-filarial antibiotic treatment more than 12 months ago 7. Resident in an endemic area for at least 5 years 8. O. volvulus patients with microfilariae skin snip positive and PCR positive for O. volvulus 9. M. perstans patients positive for microfilariae 10. PCR endemic controls, judged by absence of microfilariae, palpable onchocercoma, PCR negative for M. perstans and O. volvulus 11. Individuals should be free of other helminth infections and possess normal eosinophil frequencies (1-4%) and IgE levels (<100 IU/ml) 12. Good general health without any clinical condition requiring long-term medication 13. Normal white blood cell counts (3.5-11.3 x 10^3/μl) Previous inclusion criteria: 1. Willingness to participate in the study as evidenced by signing the Informed consent form 2. Participants will be male and female between 18-45 years old 3. BMI equal to or above 30 or below 25 4. Body weight >40 kg 5. Last intake of ivermectin at least 4 months ago 6. Last intake of anti-filarial antibiotic treatment more than 12 months ago 7. Resident in an endemic area for at least 5 years 8. O. volvulus patients with microfilariae skin snip positive and PCR positive for O. volvulus 9. M. perstans patients positive for microfilariae 10. PCR Endemic controls, judged by absence of microfilariae, palpable onchocercoma, PCR negative for M. perstans and O. volvulus. 11. Individuals should be free of other helminth infections and possess normal eosinophil frequencies (1-4%) and IgE levels (<100 IU/ml). 12. Good general health without any clinical condition requiring long-term medication 13. Normal white blood cell counts (4.4-11.3 x 10^3/μl) |
| Key exclusion criteria | 1. Pregnancy (dipstick pregnancy test) 2. Lactating mothers 3. Last intake of ivermectin (IVM) less than 4 months ago 4. Intake of anti-filarial antibiotic treatment (tetracycline) less than 12 months ago 5. Evidence of tuberculosis (clinical aspects) 6. Evidence of clinical aspects of HIV infection 7. Evidence/previous diagnosis of chronic diseases (urolithiasis, liver cirrhosis, congestive heart failure, chronic lung diseases, chronic infections other than filariae, viral hepatitis) 8. Evidence of autoimmune diseases (except for diabetes) and allergies 9. Evidence of acute infection (haematuria, cough, fever). Evidence of clinically significant neurological, cardiac, pulmonary, metabolic, rheumatologic or renal disease as far as can be assessed by history of individuals, physical examination, and/or laboratory examinations 10. Childbearing potential and not willing or able to use methods to prevent pregnancy for the entire treatment duration in addition to hormonal contraception (e.g. condoms) unless surgically sterilized/ hysterectomized or any other criteria considered sufficiently reliable by the investigator. 11. Behavioural, cognitive or psychiatric disease that in the opinion of the trial clinician affects the ability of the participant to understand and cooperate with the study protocol Added 24/01/2022: 12. Laboratory values that will lead to exclusion: 12.1. Haemoglobin <8 g/dl 12.2. Neutrophil count <500/µl* 12.3. Platelet count <100,000/µl 12.4. Creatinine >2 times upper limit of normal 12.5. AST (GOT) >2 times upper limit of normal 12.6. ALT (GPT) >2 times upper limit of normal 12.7. γ-GT >2 times upper limit of normal |
| Date of first enrolment | 01/01/2020 |
| Date of final enrolment | 30/06/2023 |
Locations
Countries of recruitment
- Cameroon
Study participating centre
N/A
Cameroon
Sponsor information
University/education
Department of Microbiology and Parasitology (DMP)
University of Buea
Buea
P.O.Box 63
Cameroon
| Phone | +237 694727715 |
|---|---|
| samwandji@gmail.com | |
"ROR" |
https://ror.org/041kdhz15 |
Funders
Funder type
Research organisation
Government organisation / National government
- Alternative name(s)
- German Research Association, German Research Foundation, DFG
- Location
- Germany
Results and Publications
| Intention to publish date | 01/01/2026 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publications in a high-impact peer-reviewed journal: 1. Metabolic immune profile of the lean and obese subjects with and without filarial infections 2. Intervention study that addresses the question of whether treatment for filarial infection aggravates the risk of type 2 diabetes |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | 02/06/2023 | 05/06/2023 | Yes | No |
Editorial Notes
23/01/2025: The following changes were made to the study record:
1. Total final enrolment was changed from 839 to 2171.
2. The intention to publish date was changed from 01/01/2025 to 01/01/2026.
16/07/2024: The intention to publish date was changed from 01/01/2024 to 01/01/2025.
11/09/2023: The following changes were made to the trial record:
1. The total final enrolment was added.
2. The intention to publish date was changed from 01/01/2023 to 01/01/2024.
05/06/2023: Publication reference added.
10/01/2023: The following changes were made to the trial record:
1. The target number of participants was changed from '400 M. perstans-infected individuals, 400 O. volvulus-infected subjects, 400 endemic normal subjects' to '400 M. perstans-infected individuals, 400 O. volvulus-infected subjects, 400 Loa loa-infected subjects, 400 endemic normal subjects'
2. The recruitment end date was changed from 31/12/2022 to 30/06/2023.
24/01/2022: The following changes were made to the trial record:
1. The ethics approval, interventions and primary outcome measures, inclusion and exclusion criteria were updated.
2. The study design was changed from 'Interventional randomized controlled open-label pilot trial' to 'Interventional controlled open-label pilot trial'.
3. The recruitment end date was changed from 31/12/2020 to 31/12/2022.
02/12/2019: Trial’s existence confirmed by Deutsche Forschungsgemeinschaft
