Clinical trial NCT03337152: Assessing a Risk Model for G6PD Deficiency
Official title: Developing a Methodology to Assess 8-aminoquinoline Associated Haemolytic Risk in Females Heterozygous for G6PD in Endemic Populations
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Malaria, Vivax
G6PD Deficiency
Lead sponsor: PATH
Sponsor class: OTHER
Collaborators: name: Mahidol Oxford Tropical Medicine Research Unit
First posted: 2017-11-08
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized into one of two arms. 1a will receive primaquine for 14 days, and Arm 1b will receive chloroquine for 3 days and concomitant primaquine for 14 days.
Primary purpose: TREATMENT

Brief summary: A clinical study designed to develop and inform an individual risk of hemolysis model based on individual red blood cell G6PD levels. Volunteers who are eligible to treatment with primaquine as per national guidelines and with confirmed normal G6PD levels as per the fluorescent spot test will be exposed to treatment regimens of either primaquine alone for 14 days or 3 day chloroquine with concomitant primaquine for 14 days. The volunteers will be followed intensively during treatment and for 14 days after treatment for haematologic measures, G6PD quantification, and drug level assays.

Detailed description: Open label, randomized trial with 72 total participants assigned to one of two treatment arms. Each arm will have 36 participants comprised of 12 males hemizygous for wildtype G6PD, 12 females homozygous for wildtype G6PD, and 12 females heterozygous for G6PD with a normal fluorescent spot test (FST) (G6PD genotype abnormal with G6PD activity ≥40% and ≤80% of normal). Arm 1a will receive primaquine for 14 days, and Arm 1b will receive chloroquine for 3 days and concomitant primaquine for 14 days. All participants will be healthy volunteers without severe G6PD deficiency who will be followed for two weeks after completing their study drug dosing. Pregnant women and those breastfeeding will be excluded. Venous blood samples will be taken at regular intervals for haematologic measures, G6PD quantification, and drug level assays. G6PD levels will be measured both by spectrophotometry to provide whole blood G6PD levels normalized for hemoglobin, as well by flow cytometry to to provide red blood cell G6PD distributions throughout the treatment and post treatment. Changes in the G6PD distributions will be modeled, incorporating other critical haematological indicators collected throughout the study too.

Eligibility criteria: Inclusion Criteria:

* Previous G6PD test at Shoklo Malaria Research Unit (SMRU) clinic with one of following results: 1) G6PD homozygous wildtype females (G6PD genotype normal) 2) G6PD heterozygous females with a normal FST (G6PD genotype abnormal with G6PD activity ≥40% and ≤80% of normal ) 3) G6PD hemizygous wildtype males (G6PD genotype normal)
* Willing to participate and sign informed consent form
* Willing to allow donated samples to be used in future research
* Aged ≥18 years
* Ability (in the investigators' opinion) and willing to comply with all study requirements

Exclusion Criteria:

All participants:

* Malaria or other illness
* Recent history (within 20 days) of anti-malarial treatment
* History of allergy or adverse reaction to chloroquine or primaquine
* Blood transfusion in the past 3 months
* G6PD activity less than 40% normal activity or 3.00 IU/gHb by the quantitative G6PD spectrophotometric assay
* Haemoglobin ≤10 g/dL
* Presence of any condition which in the judgment of the investigator would place the subject at undue risk or interfere with the results of the study

Female participants only:

* Pregnancy at the time of screening
* Breastfeeding

Primary outcomes:
measure: Change in Haemoglobin
timeFrame: 28 days after enrollment
measure: Change in G6PD Concentration
timeFrame: 28 days after enrollment
Secondary outcomes:
measure: Significance of CYP2D6
timeFrame: 28 days after enrollment
measure: Association of Drug Levels
timeFrame: Days 1,2,3,5,7,9,11,14,17,21
measure: Serious Adverse Events
timeFrame: 28 days after enrollment
measure: Significance of Reticulocyte Count
timeFrame: Days 1,2,3,5,7,9,11,14,17,21
measure: Significance of Urobilinogen Levels
timeFrame: Days 1,2,3,5,7,9,11,14,17,21
Other outcomes:
Locations:
city: Mae Sot
country: Thailand
facility: Shoklo Malaria Research Unit (SMRU)
Study officials:
affiliation: Shoklo Malaria Research Unit (SMRU), Mahidol-Oxford Tropical Medicine Research Unit
name: François Nosten, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: