Impact of Transferrin Saturation Guided Maintenance Treatment on Quality of Life in HFE Haemochromatosis

NCT ID: NCT04779593

Last Updated: 2023-01-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

240 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-07-02

Study Completion Date

2027-01-31

Brief Summary

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Patients in maintenance treatment for HFE hemochromatosis since at least one year will be included in a two year study period and randomized in two groups experimental and control group. Because proton pump inhibitors are widely used as chronic medication, and because they can significantly modify iron absorption, patients will be stratified according to the use of proton pump inhibitors and gender. A first bloodletting will be performed at inclusion with the same volume as usually performed by the patients. Results of the biological test performed at this visit will guide the time schedule and volume of the next bloodletting according to randomization group (patients treated with bloodletting according to current guidelines "ferritin alone" versus patients treated with bloodletting according to "transferrin saturation and serum ferritin").Blood count and iron metabolism parameters will be performed at each bloodletting and follow-up visits. Time schedule and volume of bloodletting will be adjusted to biological results after each follow-up visit. Volume and schedule for bloodlettings will be determined according to guidelines specifically designed for this study to assure harmonization of treatment management, and centrally validated through the recording of the biological tests in the electronic Case Report Form which will provide the investigator with the volume and schedule of the next bloodletting. There will be two ways of treatment modification: either change of schedule or volume of bloodletting. Patients will undergo follow-up visit every six months with clinical examination, questionnaires at J0, M12 and M24 (SF-36; AIMS2-SF, WOMAC, EQ-5D-5L), and biological test. For health economics analysis, data will be obtained thanks to a dedicated extraction from SNDS database SNDS database will allow to gather hospital stays, visits, and other healthcare-related costs as well as vital status (date (month/year) of death) and cause of death. A de-identified copy of the clinical database, restricted to the relevant variables, will be sent for semideterministic matching purpose with SNDS extraction using four key variables: gender, same date (month/year) of birth, same date (day/month/year) of visit for bloodletting; pending, of course, regulatory authorization.

Detailed Description

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Conditions

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Haemochromatosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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experimental group

Patients treated with bloodletting according to "transferrin saturation and serum ferritin".

Group Type EXPERIMENTAL

Clinical examination

Intervention Type OTHER

Clinical data will be recorded (general clinical examination, height, weight, blood pressure,heart beat, alcohol and tobacco consumption, antecedent) as well as concurrent medication at each follow-up visit.

SF36 questionnaire

Intervention Type OTHER

At D0, M12 and M24. This 36 item patient reported survey of patient's health is the most commonly used and validated health survey instrument for appraising quality of life.

Items are grouped in 8 scaled scores exploring multiple dimension of global health (vitality, physical functioning, bodily pain, general health, perceptions, physical role functioning, emotional role functioning, social role functioning, mental health).

Scoring will be performed as recommended by the SF-36 instruction manual to create the eight scale scores. Furthermore, these subscales sum to obtain the total SF-36 score and will be summarized into two composite scores (physical and mental quality of life).

AIMS2_SF questionnaire

Intervention Type OTHER

At D0, M12 and M24. The Arthritis Impact Measurement Scales 2 Short Form (AIMS2-SF) is a specific tool to measure changes in global health, pain, mobility and social function in patients with arthritis. It was described in 1992 in patients with rheumatoid arthritis and osteoarthritis and include 26 items that are summarized in scales according to a predefined scoring system: mobility, physical activity (walking, bending, lifting), dexterity, household activity (managing money and medications, housekeeping), social activities, activities of daily living, pain, depression, and anxiety. The French translation has been validated and this questionnaires has been widely used in the rheumatology field to assess quality of life of patients with arthritis. Because HFE related arthropathy is very similar to osteoarthritis this questionnaire is ought to be adequate in this setting.

WOMAC questionnaire

Intervention Type OTHER

At D0, M12 and M24. The Western Ontario and McMaster Universities Arthritis Index (WOMAC) is a widely used questionnaires specifically assessing lower limb (hips and knee) osteoarthritis. It measures five items for pain, two for stiffness and 17 for functional limitation and had been translated in French.

EQ-5D-5L questionnaire

Intervention Type OTHER

At D0, M12 and M24. The EQ-5D is a standardized instrument which evaluates the generic quality of life (http://www.euroqol.org/). It is a preference-based health-related quality of life measure with one question for each of the five dimensions that include mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The answers given to EQ-5D permit to find 243 health states that can be converted into utility score anchored at 0 for death and 1 for perfect health. EQ-5D is an instrument developed in Europe, widely used in cost-utility analysis. It has been validated in a representative sample of French population.

Blood Sample Complete blood count

Intervention Type BIOLOGICAL

Blood Sample Complete blood count at D0, M6, M12, M18 and M24/end follow-up visit

Blood Sample Iron panel

Intervention Type BIOLOGICAL

Blood Sample Iron panel (serum ferritin, serum iron and serum transferrin to determine transferrin saturation according to randomization group (at M6, M12 and M18) at D0, M6, M12, M18 and M24/end follow-up visit and at each bloodletting.

Blood Sample Fasting Glucose

Intervention Type BIOLOGICAL

Blood Sample Fasting Glucose at D0 and M24/end follow-up visit

Blood sample lipid panel

Intervention Type BIOLOGICAL

Blood sample lipid panel (total cholesterol, triglycerides, HDL, LDL) at D0 and M24/end follow-up visit

Blood sample liver panel

Intervention Type BIOLOGICAL

Blood sample liver panel (total bilirubin, Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma-Glutamyl Transferase) at D0 and M24/end follow-up visit

Blood sample C reactive protein

Intervention Type BIOLOGICAL

Blood sample C reactive protein at D0 and M24/end follow-up visit

BioBank

Intervention Type BIOLOGICAL

Blood sample will be collected for BioBank at D0, M12 and M24.

Medico-economical

Intervention Type OTHER

Medico-economic data will be collected at each follow up visit.

Bloodletting - experimental group

Intervention Type PROCEDURE

Patients treated with bloodletting according to "transferrin saturation and serum ferritin". Patients will undergo bloodletting with a goal of maintaining a serum transferrin saturation equal or lower than 50 % and a serum ferritin lower than the upper limit of the normal range (300 g/L for men and 200 g/L for women).A first bloodletting will be performed at inclusion with the same volume as usually performed by the patients.Results of the biological test performed at this visit will guide the time schedule and volume of the next bloodletting according to randomization group. Time schedule and volume of bloodletting will be adjusted to biological results after each follow-up visit.

control group

Patients treated with bloodletting according to current guidelines "ferritin alone"

Group Type ACTIVE_COMPARATOR

Clinical examination

Intervention Type OTHER

Clinical data will be recorded (general clinical examination, height, weight, blood pressure,heart beat, alcohol and tobacco consumption, antecedent) as well as concurrent medication at each follow-up visit.

SF36 questionnaire

Intervention Type OTHER

At D0, M12 and M24. This 36 item patient reported survey of patient's health is the most commonly used and validated health survey instrument for appraising quality of life.

Items are grouped in 8 scaled scores exploring multiple dimension of global health (vitality, physical functioning, bodily pain, general health, perceptions, physical role functioning, emotional role functioning, social role functioning, mental health).

Scoring will be performed as recommended by the SF-36 instruction manual to create the eight scale scores. Furthermore, these subscales sum to obtain the total SF-36 score and will be summarized into two composite scores (physical and mental quality of life).

AIMS2_SF questionnaire

Intervention Type OTHER

At D0, M12 and M24. The Arthritis Impact Measurement Scales 2 Short Form (AIMS2-SF) is a specific tool to measure changes in global health, pain, mobility and social function in patients with arthritis. It was described in 1992 in patients with rheumatoid arthritis and osteoarthritis and include 26 items that are summarized in scales according to a predefined scoring system: mobility, physical activity (walking, bending, lifting), dexterity, household activity (managing money and medications, housekeeping), social activities, activities of daily living, pain, depression, and anxiety. The French translation has been validated and this questionnaires has been widely used in the rheumatology field to assess quality of life of patients with arthritis. Because HFE related arthropathy is very similar to osteoarthritis this questionnaire is ought to be adequate in this setting.

WOMAC questionnaire

Intervention Type OTHER

At D0, M12 and M24. The Western Ontario and McMaster Universities Arthritis Index (WOMAC) is a widely used questionnaires specifically assessing lower limb (hips and knee) osteoarthritis. It measures five items for pain, two for stiffness and 17 for functional limitation and had been translated in French.

EQ-5D-5L questionnaire

Intervention Type OTHER

At D0, M12 and M24. The EQ-5D is a standardized instrument which evaluates the generic quality of life (http://www.euroqol.org/). It is a preference-based health-related quality of life measure with one question for each of the five dimensions that include mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The answers given to EQ-5D permit to find 243 health states that can be converted into utility score anchored at 0 for death and 1 for perfect health. EQ-5D is an instrument developed in Europe, widely used in cost-utility analysis. It has been validated in a representative sample of French population.

Blood Sample Complete blood count

Intervention Type BIOLOGICAL

Blood Sample Complete blood count at D0, M6, M12, M18 and M24/end follow-up visit

Blood Sample Iron panel

Intervention Type BIOLOGICAL

Blood Sample Iron panel (serum ferritin, serum iron and serum transferrin to determine transferrin saturation according to randomization group (at M6, M12 and M18) at D0, M6, M12, M18 and M24/end follow-up visit and at each bloodletting.

Blood Sample Fasting Glucose

Intervention Type BIOLOGICAL

Blood Sample Fasting Glucose at D0 and M24/end follow-up visit

Blood sample lipid panel

Intervention Type BIOLOGICAL

Blood sample lipid panel (total cholesterol, triglycerides, HDL, LDL) at D0 and M24/end follow-up visit

Blood sample liver panel

Intervention Type BIOLOGICAL

Blood sample liver panel (total bilirubin, Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma-Glutamyl Transferase) at D0 and M24/end follow-up visit

Blood sample C reactive protein

Intervention Type BIOLOGICAL

Blood sample C reactive protein at D0 and M24/end follow-up visit

Bloodletting - control group

Intervention Type PROCEDURE

Patients treated with bloodletting according to current guidelines (ferritin alone). Patient will undergo bloodletting with a goal of maintaining a serum ferritin equal or lower than 50 g/L according to current clinical practice guidelines (French and European).A first bloodletting will be performed at inclusion with the same volume as usually performed by the patients.Results of the biological test performed at this visit will guide the time schedule and volume of the next bloodletting according to randomization group. Time schedule and volume of bloodletting will be adjusted to biological results after each follow-up visit.

BioBank

Intervention Type BIOLOGICAL

Blood sample will be collected for BioBank at D0, M12 and M24.

Medico-economical

Intervention Type OTHER

Medico-economic data will be collected at each follow up visit.

Interventions

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Clinical examination

Clinical data will be recorded (general clinical examination, height, weight, blood pressure,heart beat, alcohol and tobacco consumption, antecedent) as well as concurrent medication at each follow-up visit.

Intervention Type OTHER

SF36 questionnaire

At D0, M12 and M24. This 36 item patient reported survey of patient's health is the most commonly used and validated health survey instrument for appraising quality of life.

Items are grouped in 8 scaled scores exploring multiple dimension of global health (vitality, physical functioning, bodily pain, general health, perceptions, physical role functioning, emotional role functioning, social role functioning, mental health).

Scoring will be performed as recommended by the SF-36 instruction manual to create the eight scale scores. Furthermore, these subscales sum to obtain the total SF-36 score and will be summarized into two composite scores (physical and mental quality of life).

Intervention Type OTHER

AIMS2_SF questionnaire

At D0, M12 and M24. The Arthritis Impact Measurement Scales 2 Short Form (AIMS2-SF) is a specific tool to measure changes in global health, pain, mobility and social function in patients with arthritis. It was described in 1992 in patients with rheumatoid arthritis and osteoarthritis and include 26 items that are summarized in scales according to a predefined scoring system: mobility, physical activity (walking, bending, lifting), dexterity, household activity (managing money and medications, housekeeping), social activities, activities of daily living, pain, depression, and anxiety. The French translation has been validated and this questionnaires has been widely used in the rheumatology field to assess quality of life of patients with arthritis. Because HFE related arthropathy is very similar to osteoarthritis this questionnaire is ought to be adequate in this setting.

Intervention Type OTHER

WOMAC questionnaire

At D0, M12 and M24. The Western Ontario and McMaster Universities Arthritis Index (WOMAC) is a widely used questionnaires specifically assessing lower limb (hips and knee) osteoarthritis. It measures five items for pain, two for stiffness and 17 for functional limitation and had been translated in French.

Intervention Type OTHER

EQ-5D-5L questionnaire

At D0, M12 and M24. The EQ-5D is a standardized instrument which evaluates the generic quality of life (http://www.euroqol.org/). It is a preference-based health-related quality of life measure with one question for each of the five dimensions that include mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The answers given to EQ-5D permit to find 243 health states that can be converted into utility score anchored at 0 for death and 1 for perfect health. EQ-5D is an instrument developed in Europe, widely used in cost-utility analysis. It has been validated in a representative sample of French population.

Intervention Type OTHER

Blood Sample Complete blood count

Blood Sample Complete blood count at D0, M6, M12, M18 and M24/end follow-up visit

Intervention Type BIOLOGICAL

Blood Sample Iron panel

Blood Sample Iron panel (serum ferritin, serum iron and serum transferrin to determine transferrin saturation according to randomization group (at M6, M12 and M18) at D0, M6, M12, M18 and M24/end follow-up visit and at each bloodletting.

Intervention Type BIOLOGICAL

Blood Sample Fasting Glucose

Blood Sample Fasting Glucose at D0 and M24/end follow-up visit

Intervention Type BIOLOGICAL

Blood sample lipid panel

Blood sample lipid panel (total cholesterol, triglycerides, HDL, LDL) at D0 and M24/end follow-up visit

Intervention Type BIOLOGICAL

Blood sample liver panel

Blood sample liver panel (total bilirubin, Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma-Glutamyl Transferase) at D0 and M24/end follow-up visit

Intervention Type BIOLOGICAL

Blood sample C reactive protein

Blood sample C reactive protein at D0 and M24/end follow-up visit

Intervention Type BIOLOGICAL

Bloodletting - control group

Patients treated with bloodletting according to current guidelines (ferritin alone). Patient will undergo bloodletting with a goal of maintaining a serum ferritin equal or lower than 50 g/L according to current clinical practice guidelines (French and European).A first bloodletting will be performed at inclusion with the same volume as usually performed by the patients.Results of the biological test performed at this visit will guide the time schedule and volume of the next bloodletting according to randomization group. Time schedule and volume of bloodletting will be adjusted to biological results after each follow-up visit.

Intervention Type PROCEDURE

BioBank

Blood sample will be collected for BioBank at D0, M12 and M24.

Intervention Type BIOLOGICAL

Medico-economical

Medico-economic data will be collected at each follow up visit.

Intervention Type OTHER

Bloodletting - experimental group

Patients treated with bloodletting according to "transferrin saturation and serum ferritin". Patients will undergo bloodletting with a goal of maintaining a serum transferrin saturation equal or lower than 50 % and a serum ferritin lower than the upper limit of the normal range (300 g/L for men and 200 g/L for women).A first bloodletting will be performed at inclusion with the same volume as usually performed by the patients.Results of the biological test performed at this visit will guide the time schedule and volume of the next bloodletting according to randomization group. Time schedule and volume of bloodletting will be adjusted to biological results after each follow-up visit.

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* \- Patients treated with iron chelators;
* Patients treated with erythroid growth factors (erythropoietin);
* Patient with excessive alcohol consumption (\> 20g/day and \> 30 g/day for women and men respectively);
* Patients with chronic haematological condition;
* Patients having uncontrolled chronic blood loss (of digestive or gynaecological origin);
* Patients with chronic kidney failure;
* Patients with a diagnosis of cancer or history of cancer in the last year;
* Pregnancy or breast feeding.
* Patient who are included in another research protocol
* Adults legally protected (judicial protection, guardianship, or supervision), persons deprived of their freedom.
* with C282Y homozygous HFE hemochromatosis;
* having finished the initial phase of HFE hemochromatosis treatment and in maintenance treatment for at least one year;
* having signed an informed consent form.

Exclusion Criteria

* Patients treated with iron chelators;
* Patients treated with erythroid growth factors (erythropoietin);
* Patient with excessive alcohol consumption (\> 20g/day and \> 30 g/day for women and men respectively);
* Patients with chronic haematological condition;
* Patients having uncontrolled chronic blood loss (of digestive or gynaecological origin);
* Patients with chronic kidney failure;
* Patients with a diagnosis of cancer or history of cancer in the last year;
* Pregnancy or breast feeding.
* Patient who are included in another research protocol
* Adults legally protected (judicial protection, guardianship, or supervision), persons deprived of their freedom.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Rennes University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Hopital Avicenne

Bobigny, , France

Site Status RECRUITING

CHU Dupuytren

Limoges, , France

Site Status RECRUITING

GHBS site du Scorff

Lorient, , France

Site Status RECRUITING

GHRMSA - Hôpital Emile Muller

Mulhouse, , France

Site Status RECRUITING

CHR Orléans

Orléans, , France

Site Status RECRUITING

Hôpital Européen Georges Pompidou

Paris, , France

Site Status NOT_YET_RECRUITING

CHU Rennes

Rennes, , France

Site Status RECRUITING

CH Yves le Foll

Saint-Brieuc, , France

Site Status RECRUITING

CH de St Malo

St-Malo, , France

Site Status RECRUITING

Hôpital Rangueil

Toulouse, , France

Site Status RECRUITING

Centre hospitalier Bretagne Atlantique

Vannes, , France

Site Status RECRUITING

Hôpital Paul Brousse

Villejuif, , France

Site Status RECRUITING

Countries

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France

Facility Contacts

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Nathalie GANNE

Role: primary

01 48 95 55 55 ext. +33

Véronique LOUSTAUD-RATTI

Role: primary

05. 55. 05. 66. 84 ext. +33

Florent EHRHARD

Role: primary

02 97 06 94 98 ext. +33

Bernard DRENOU

Role: primary

03 89 64 77 55 ext. +33

Xavier CAUSSE

Role: primary

02 38 22 96 58

Prunelle GETTEN

Role: primary

01 56 09 53 41 ext. +33

Prunelle GETTEN

Role: backup

Edouard Bardou-Jacquet

Role: primary

02.99.28.53.08 ext. +33

Antonia LE GRUYER

Role: primary

02 96 01 73 78 ext. +33

Christine Beusnel

Role: primary

02 99 21 27 83 ext. +33

Christophe BUREAU

Role: primary

05 61 32 36 86 ext. +33

Gaëlle BILLET

Role: primary

02 97 01 99 01 ext. +33

Rodolphe Sobesky

Role: primary

01 45 59 67 81 ext. +33

Rodolphe Sobesky

Role: backup

Other Identifiers

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35RC19_8985_Quali-SAT

Identifier Type: -

Identifier Source: org_study_id

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