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

NCT07817069 | Recruiting DMC

• 1 other identifier: CEFMS 136/2022
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Obesity & Overweight; Abdominal Obesity; Treatment Resistant Schizophrenia

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Body weight

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

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

• Waist circumference

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

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

Secondary Outcomes (8)

• Other anthropometric measurements

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

• Body composition

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

• Concentration of Triglycerides

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

• Concentration of High-Density Lipoprotein Cholesterol

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

• Concentration of Low-Density Lipoprotein Cholesterol

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

Study Arms (1)

Treatment-resistant schizophrenia patients' with clozapine-induced obesity

EXPERIMENTAL

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

The Nitraria retusa arm DIETARY_SUPPLEMENT

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).

Treatment-resistant schizophrenia patients' with clozapine-induced obesity

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 (BMI \> 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Faculty of Medicine, Sousse: lead
• University of Tsukuba: collaborator

Study Sites (1)

Farhat Hached University Hospital

Sousse, 4000, Tunisia

RECRUITING

Related Publications (4)

• 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.

  PMID: 35937836 BACKGROUND

• 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.

  PMID: 37630839 BACKGROUND

• 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.

  PMID: 38276555 BACKGROUND

• 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.

  PMID: 33716966 BACKGROUND

MeSH Terms

Conditions

Schizophrenia, Treatment-Resistant; Obesity; Overweight; Obesity, Abdominal; Metabolic Syndrome

Condition Hierarchy (Ancestors)

Schizophrenia; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases

Study Officials

• Saad Saguem, Professor

  Faculty of Medicine, Sousse

  STUDY DIRECTOR

Central Study Contacts

Bochra Nourhène Saguem, M.D.; Associate Professor

CONTACT

+21655617728; saguem.bochra@gmail.com

Saad Saguem, Professor

CONTACT

+21653673851; khaled_saguem@yahoo.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Psychiatrist, CBT psychotherapist, Music Therapist at the Psychiatry Department, Farhat Hached Hospital, Sousse; Associate professor in psychiatry, Faculty of Medicine of Sousse

Study Record Dates

• First Submitted: September 3, 2026
• First Posted: September 14, 2026
• Study Start: January 3, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: September 14, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: At the end of the trial

Locations

TU (1)