Condition category
Infections and Infestations
Date applied
27/11/2019
Date assigned
02/12/2019
Last edited
02/12/2019
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Not yet recruiting

Plain English Summary

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 45 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 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?
Half of the M. perstans infected patients will randomly be treated with 200mg of doxycycline daily for 6 weeks, which will eliminate the filarial infection. The other half of the M. perstans infected patients will not be treated against the filarial infection, as Mansonella does not cause pathology. The benefit of the Mansonella infected patients is a scientific one, as it will clarify whether clearance of the Mansonella infection will impact the development of diabetes and effect future filarial treatment programs. Endemic controls and O. volvulus infected patients will take part in 4 rounds of 150µg/kg ivermectin (Mectizan) in three-month intervals in the process of a mass drug administration (MDA) for the whole community. Treatment of onchocerciasis patients with ivermectin is known to stop the release of the filarial offspring for up to one year. As the pathology in onchocerciasis is driven by the filarial offspring, this will reduce pathology. All subjects will also receive single doses of 400mg albendazole every 3 months with a total of 4 treatments.
Blood sample collection will occur at baseline, 12 month and 24 months. For the determination of intestinal helminths we will additionally require 3 stool samples at baseline, 12 month 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 finger tip at baseline, 12 month 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

Trial website

Contact information

Type

Scientific

Primary contact

Dr Marc Hübner

ORCID ID

http://orcid.org/0000-0001-8885-418X

Contact details

Institute for Medical Microbiology
Immunology and Parasitology
University Hospital of Bonn
Venusberg-Campus 1 Building 63
Bonn
53127
Germany
+49 228-287-19177
Huebner@uni-bonn.de

Type

Public

Additional contact

Prof Samuel Wanji

ORCID ID

http://orcid.org/0000-0003-0022-8366

Contact details

Department of Microbiology and Parasitology
Faculty of Science
University of Buea
Buea
P.O.Box 63
Cameroon
+237 694-727715
samwandji@gmail.com

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

FIMMIP HU 2144/3-1

Study information

Scientific title

Impact of human filarial infections on the metabolic and immunological profile in type 2 diabetes

Acronym

FIMMIP

Study hypothesis

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

1. Approved 10/10/2017, 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, 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

Study design

Interventional randomized controlled open label pilot trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Community

Trial type

Screening

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Human filarial infection and type 2 diabetes

Intervention

1. Patients infected with M. perstans:
Patients will be divided into lean (BMI <25) and obese (BMI ≥ 30). From each group half 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 4 rounds of 150µg/kg ivermectin (Mectizan) in three-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 4 rounds of 150µg/kg ivermectin (Mectizan) in three-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: 400mg albendazole every three months with a total of 4 treatments for groups 1, 2 and 3.

Blood sample collection will occur at baseline, 12 month and 24 months. For the determination of intestinal helminths we will additionally require 3 stool samples at baseline, 12 month 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 month 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

Phase

Not Applicable

Drug names

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
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 trial start date

01/08/2016

Overall trial end date

31/12/2026

Reason abandoned (if study stopped)

Eligibility

Participant 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 > 40kg
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)

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

400 M. perstans-infected individuals, 400 O. volvulus-infected subjects, 400 endemic normal subjects

Participant 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

Recruitment start date

01/01/2020

Recruitment end date

31/12/2020

Locations

Countries of recruitment

Cameroon

Trial participating centre

District de Sante de Manjo in Cameroon
Manjo
N/A
Cameroon

Sponsor information

Organisation

University of Buea, Faculty of Science, Department of Microbiology and Parasitology

Sponsor details

Department of Microbiology and Parasitology (DMP)
University of Buea
Buea
P.O.Box 63
Cameroon
+237 694727715
samwandji@gmail.com

Sponsor type

University/education

Website

Funders

Funder type

Research organisation

Funder name

Deutsche Forschungsgemeinschaft

Alternative name(s)

German Research Foundation, German Research Association, DFG

Funding Body Type

private sector organisation

Funding Body Subtype

Trusts, charities, foundations (both publically funded and privately funded)

Location

Germany

Results and Publications

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 statement:
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request

Intention to publish date

01/01/2023

Participant level data

Available on request

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

02/12/2019: Trial’s existence confirmed by Deutsche Forschungsgemeinschaft