ClinicalTrials.gg
RecruitingNCT07817069Updated Sep 14, 2026

Effects of Nitraria Retusa Infusion on Clozapine-induced Metabolic Side Effects

An interventional study of The Nitraria retusa arm in Treatment Resistant Schizophrenia, Obesity & Overweight and Abdominal Obesity, sponsored by Faculty of Medicine, Sousse. Recruiting at 1 site in Tunisia. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2026-09-14.

Sponsored by Faculty of Medicine, Sousse · Not applicable, Interventional, and Treatment

From the registry’s dates

  • Registered 8 months after the study started (first participant enrolled Jan 2026, registered Sep 2026).
  • Started Jan 2026; still recruiting 10 months later.
Phase
Not applicable
Study type
Interventional
Enrollment
30
Allocation
Not applicable
Ages
18 Years to 65 Years
Sex
All
01

Study summary

The primary objective of the study is to assess the efficacy and tolerability of a 90-day daily supplementation with a Nitraria retusa dried crushed leaves infusion on the iatrogenic metabolic side effects induced in patients with treatment-resistant schizophrenia following clozapine treatment.

After providing written informed consent, eligible patients with treatment-resistant schizophrenia will be invited to receive a daily Nitraria retusa extract infusion at approximately 9 PM for 90 consecutive days, as an adjunct to their usual medications. Patients will be instructed to maintain their usual diet, routine, and lifestyle throughout the study.

Clinical and biological evaluations will be conducted prospectively at baseline (T0), day 10 (T1), day 45 (T2), and day 90 (T3). Two additional assessments will be planned at day 30 and day 60 to comply with the monthly complete blood count (CBC) surveillance recommended for patients receiving clozapine. Assessments include anthropometric measures, body composition, vital signs, CBC, metabolic panels, and renal and hepatic function. All biological samples were collected after a 12-hour fast.

Read the detailed description

A pilot, pre-experimental study will be conducted.

  1. Study population Patients will be recruited from the outpatient Department of Psychiatry at Farhat Hached Hospital (Sousse, Tunisia). Inclusion criteria are: (1) a diagnosis of treatment-resistant schizophrenia; (2) current treatment with clozapine monotherapy or clozapine combined with other psychotropics that have a minimal documented impact on body weight; (3) demonstration of a response to clozapine, defined as a reduction of at least 20% in the total score on the Positive and Negative Syndrome Scale (PANSS) or the Brief Psychiatric Rating Scale (BPRS) after 8-12 weeks of treatment at effective therapeutic doses; and (4) presence of obesity (Body Mass Index (BMI) > 30 kg/m²) or central obesity (waist circumference > 94 cm in men and > 80 cm in women), which developed following clozapine introduction. Non-inclusion criteria are: (1) concurrent use of clozapine with other psychotropic agents that have a documented moderate-to-high influence on body weight; (2) current treatment with metformin; and (3) pregnancy or breastfeeding.
  2. Study procedure Eligible patients with treatment-resistant schizophrenia will be invited to take a daily Nitraria retusa extract infusion at approximately 9 PM for 90 consecutive days, as an adjunct to their usual medications. Patients will be instructed to maintain their usual diet, routine, and lifestyle throughout the study. Clinical and biological evaluations will be conducted prospectively at baseline (T0), day 10 (T1), day 45 (T2), and day 90 (T3).
  3. Plant material and preparation of Nitraria retusa extract Nitraria retusa was collected from saline soils in Kairouan (central Tunisia). The leaves were rinsed with water, air-dried in the shade at room temperature for 15 days, and crushed into a fine powder using a Moulinex grinder (MOULINEX SA, France). Nitraria retusa was supplied to participants in sachets containing 2,000 mg of powder. Participants were instructed to prepare the daily infusion by steeping 2,000 mg of the powder in 100 mL of boiled water for 15 minutes. Qualitative and quantitative analyses of the extract were performed using a validated ultra-high-performance liquid chromatography with diode-array detection method (UHPLC-DAD; SHIMADZU 8045).
  4. Outcome variables Outcome measures were categorized as primary and secondary.

    Primary outcomes included:

    • Body weight, measured using a calibrated scale integrated into the bioelectrical impedance analyzer, with participants wearing light clothing.
    • Waist circumference, measured at the narrowest point between the lower rib margin and the iliac crest, as an indicator of abdominal adiposity.

    Secondary outcomes encompassed:

    • Other anthropometric measurements including mid-upper arm circumference measured at the midpoint of the relaxed arm, and mid-thigh circumference measured at the midpoint of the thigh.
    • Body composition, assessed via bioelectrical impedance analysis, including body fat, muscle mass, and body water percentages.
    • Metabolic panels, including triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting blood glucose, and glycated hemoglobin (HbA1c).
    • Intervention tolerability, monitored via CBC, renal function markers, and hepatic enzymes.
  5. Ethical considerations Each participant provided written informed consent after receiving a detailed oral explanation of the study objectives and procedure, and after being given the written information sheet. Participants were also informed about their rights to withdraw at any time without any impact on the quality of their clinical care. All data were handled confidentially.
02

Conditions studied

  • Treatment Resistant Schizophrenia
  • Obesity & Overweight
  • Abdominal Obesity

Keywords

  • Nitraria retusa
  • Flavonoids
  • Clozapine
  • Treatment-resistant schizophrenia
  • Metabolic syndrome
  • Obesity
  • Antipsychotic-induced weight gain
03

In context

Schizophrenia, Treatment-Resistant

53 studies on the registry are indexed under Schizophrenia, Treatment-Resistant; 22 are open to participants now.

This study's planned enrollment of 30 is below the median of 60 across 46 interventional studies indexed under Schizophrenia, Treatment-Resistant.

Browse Schizophrenia, Treatment-Resistant studies →

Lead sponsor

Faculty of Medicine, Sousse is the lead sponsor of 23 studies on the registry; 6 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • a diagnosis of treatment-resistant schizophrenia;
  • current treatment with clozapine monotherapy or clozapine combined with other psychotropics that have a minimal documented impact on body weight; - demonstration of a response to clozapine, defined as a reduction of at least 20% in the total score on the Positive and Negative Syndrome Scale (PANSS) or the Brief Psychiatric Rating Scale (BPRS) after 8-12 weeks of treatment at effective therapeutic doses;
  • presence of obesity ( > 30 kg/m²) or central obesity (waist circumference > 94 cm in men and > 80 cm in women), which developed following clozapine introduction.
  • free informed written consent

Exclusion criteria

Exclusion Criteria:

  • concurrent use of clozapine with other psychotropic agents that have a documented moderate-to-high influence on body weight
  • current treatment with metformin
  • pregnancy or breastfeeding
  • non acceptance to take part to the study
Terms in these criteria, in plain language(1)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

BMI (body mass index)

Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.

What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.

05

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
30 participants (estimated)

Study arms

  • Experimental
    Treatment-resistant schizophrenia patients' with clozapine-induced obesity

    Inclusion criteria: (1) a diagnosis of treatment-resistant schizophrenia\]; (2) current treatment with clozapine monotherapy or clozapine combined with other psychotropics that have a minimal documented impact on body weight; (3) demonstration of a response to clozapine, defined as a reduction of at least 20% in the total score on the Positive and Negative Syndrome Scale (PANSS) or the Brief Psychiatric Rating Scale (BPRS) after 8-12 weeks of treatment at effective therapeutic doses; and (4) presence of obesity (BMI \> 30 kg/m²) or central obesity (waist circumference \> 94 cm in men and \> 80 cm in women), which developed following clozapine introduction. Non-inclusion criteria: (1) concurrent use of clozapine with other psychotropic agents that have a documented moderate-to-high influence on body weight; (2) current treatment with metformin; and (3) pregnancy or breastfeeding.

    Dietary Supplement: The Nitraria retusa arm

Interventions

  • Dietary supplementThe Nitraria retusa arm

    A daily administration of Nitraria retusa extract infusion at approximately 9 PM for 90 consecutive days, as an adjunct to patients' usual medications, while maintaining usual diet, routine, and lifestyle throughout the study. Nitraria retusa was collected from saline soils in Kairouan (central Tunisia). The leaves were rinsed with water, air-dried in the shade at room temperature for 15 days, and crushed into a fine powder using a Moulinex grinder (MOULINEX SA, France). Nitraria retusa was supplied to participants in sachets containing 2,000 mg of powder. Participants were instructed to prepare the daily infusion by steeping 2,000 mg of the powder in 100 mL of boiled water for 15 minutes. Qualitative and quantitative analyses of the extract were performed using a validated high-performance liquid chromatography method (UHPLC-DAD, SHIMADZU 8045).

06

What researchers measure

Primary outcomes

  1. Body weight

    Body weight, measured using a calibrated scale integrated into the bioelectrical impedance analyzer, with participants wearing light clothing.

    Time frame: baseline (T0), day 10 (T1), day 45 (T2), and day 90 (T3)

  2. Waist circumference

    Waist circumference, measured at the narrowest point between the lower rib margin and the iliac crest, as an indicator of abdominal adiposity.

    Time frame: baseline (T0), day 10 (T1), day 45 (T2), and day 90 (T3)

Secondary outcomes

  1. Other anthropometric measurements

    Other anthropometric measurements including mid-upper arm circumference measured at the midpoint of the relaxed arm, and mid-thigh circumference measured at the midpoint of the thigh.

    Time frame: baseline (T0), day 10 (T1), day 45 (T2), and day 90 (T3)

  2. Body composition

    Body composition, assessed via bioelectrical impedance analysis, including body fat percentage, muscle mass percentage, and body water percentage.

    Time frame: baseline (T0), day 10 (T1), day 45 (T2), and day 90 (T3)

  3. Concentration of Triglycerides

    Fasting serum triglyceride (TG) concentration

    Time frame: baseline (T0), day 10 (T1), day 45 (T2), and day 90 (T3)

  4. Concentration of High-Density Lipoprotein Cholesterol

    Fasting serum High-Density Lipoprotein Cholesterol (HDL-C) concentration

    Time frame: baseline (T0), day 10 (T1), day 45 (T2), and day 90 (T3)

  5. Concentration of Low-Density Lipoprotein Cholesterol

    Fasting serum Low-Density Lipoprotein Cholesterol (LDL-C) concentration

    Time frame: baseline (T0), day 10 (T1), day 45 (T2), and day 90 (T3)

  6. Fasting Blood Glucose Level

    Fasting plasma glucose concentration

    Time frame: baseline (T0), day 10 (T1), day 45 (T2), and day 90 (T3)

  7. Glycated Hemoglobin (HbA1c) Level

    Percentage of glycated hemoglobin (HbA1c)

    Time frame: baseline (T0) and day 90 (T3)

  8. Incidence of treatment-emergent abnormalities in Complete Blood Count, renal function, and hepatic Enzymes

    Number of participants with clinically significant treatment-emergent abnormalities in complete blood count (CBC), renal function markers, or hepatic enzymes during the 90-day intervention period.

    Time frame: baseline (T0), day 10 (T1), day 45 (T2), and day 90 (T3)

07

Study locations

1 of 1 sites recruiting
  • Farhat Hached University Hospital
    Sousse, 4000, Tunisia
    Recruiting
    • Bochra Nourhène Saguem, M.D.; Associate Professor · Contactsaguem.bochra@gmail.com · +21655617728
    • Jaâfar Nakhli, Professor · Sub investigator
    • Bochra Nourhène Saguem, M.D.; Associate Professor · Principal investigator
08

References and documents

Publications

  • Yao J, Zhang Y, Zhao J, Wang XZ, Lin YP, Sun L, Lu QY, Fan GJ. Efficacy of flavonoids-containing supplements on insulin resistance and associated metabolic risk factors in overweight and obese subjects: a systematic review and meta-analysis of 25 randomized controlled trials. Front Endocrinol (Lausanne). 2022 Jul 22;13:917692. doi: 10.3389/fendo.2022.917692. eCollection 2022. PubMed 35937836 ↗
  • Laouani A, Nasrallah H, Sassi A, Ferdousi F, Kalai FZ, Hasni Y, Limem K, Isoda H, Saguem S. Exploring the Effects of Short-Term Daily Intake of Nitraria retusa Tea on Lipid Profile: A Pre-Post, Uncontrolled Pilot Study in Both Healthy and Overweight/Obese Adults. Nutrients. 2023 Aug 20;15(16):3649. doi: 10.3390/nu15163649. PubMed 37630839 ↗
  • Laouani A, Nasrallah H, Sassi A, Ferdousi F, Kalai FZ, Hasni Y, Isoda H, Saguem S. Antiobesity and Hypolipidemic Potential of Nitraria retusa Extract in Overweight/Obese Women: A Randomized, Double-Blind, Placebo-Controlled Pilot Study. Nutrients. 2024 Jan 21;16(2):317. doi: 10.3390/nu16020317. PubMed 38276555 ↗
  • Yuen JWY, Kim DD, Procyshyn RM, Panenka WJ, Honer WG, Barr AM. A Focused Review of the Metabolic Side-Effects of Clozapine. Front Endocrinol (Lausanne). 2021 Feb 25;12:609240. doi: 10.3389/fendo.2021.609240. eCollection 2021. PubMed 33716966 ↗

Individual participant data

Plan to share: Yes — The investigators plan to share anonymous results of the primary and secondary outcome variables of each study participant in form of Tables.

Supporting information: Clinical study report

Time frame: At the end of the trial

09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Started Jan 2026 (actual). Primary completion is estimated for Dec 2028, 35 months after the start.

How these figures are worked out, and which studies are left out of them.

Registered
Sep 3, 2026
First posted
Sep 14, 2026
StartActual
Jan 3, 2026
Primary completionEst.
Dec 2028
CompletionEst.
Dec 2028
Last update
Sep 14, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Sep 14, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT07817069
Lead sponsor
Faculty of Medicine, Sousse
Collaborators
University of Tsukuba
Responsible party
Bochra Nourhène Saguem (Psychiatrist, CBT psychotherapist, Music Therapist at the Psychiatry Department, Farhat Hached Hospital, Sousse; Associate professor in psychiatry, Faculty of Medicine of Sousse, Faculty of Medicine, Sousse) — Principal investigator
First posted
Sep 14, 2026
Start date
Jan 3, 2026
Primary completion
Dec 2028 (estimated)
Completion
Dec 2028 (estimated)
Last update
Sep 14, 2026

Study contacts

Bochra Nourhène Saguem, M.D.; Associate Professor
Contact
saguem.bochra@gmail.com
+21655617728
Saad Saguem, Professor
Contact
khaled_saguem@yahoo.fr
+21653673851
Saad Saguem, Professor
study director · Faculty of Medicine, Sousse

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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