Disposition Kinetics of Dolutegravir Among People Living With HIV With Major Depression in Nigeria

NCT07110831 | Not Yet Recruiting Phase 4 DMC

• 2 other identifiers: UI/EC/22/0242K43TW011995
• Study Type: interventional
• Target: 168
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to find out the usefulness and well-being of people when drugs for treating depression (fluoxetine) and HIV (dolutegravir) are used together. It will also learn about how safe it is to take fluoxetine and dolutegravir together by the people living with HIV (PLWH). The main questions it aims to answer are:

• Does fluoxetine (antidepressant) make participants taking anti-HIV (dolutegravir) feel better?
• What medical problems do participants have when taking fluoxetine and dolutegravir together?
• Does what people inherit from their parents affect the effectiveness and medical problems that participants have when taking fluoxetine and dolutegravir together? Researchers will compare depression treatments, fluoxetine and psychological treatment \[cognitive behavioural therapy (CBT)\] together to psychological treatment (CBT) alone among adults PLWH on anti-HIV drug (dolutegravir). Participants on anti-HIV dolutegravir having depression will:
• Take both fluoxetine (daily) and CBT together or CBT alone for 3 months
• Visit the clinic once every week in the first month, then once every 2 weeks for checkups and tests including blood tests
• Keep a diary of their symptoms and other complaints

Conditions

Depression; HIV

Keywords

Depression; Depressive Disorder, Major; HIV; Antidepressive Agents; Selective Serotonin Reuptake Inhibitors; Fluoxetine; Antiretroviral Therapy, Highly Active; Dolutegravir; Pharmacokinetics

Outcome Measures

Primary Outcomes (7)

• Mean change in the Hamilton Depression Rating Scale (HAM-D) scores from baseline to 12 weeks

  The total HAM-D scores provide an indication of depression and, over time, a guide to evaluate response and recovery. The higher the HAM-D scores, the higher the severity of depression. HAM-D is graded as follows None 0-7 Mild 8-16 Moderate 17-23 Severe ≥ 24

  Baseline to the end of treatment at 12 weeks

• Mean changes in the AUC of dolutegravir

  The effect of chronic administration of fluoxetine on the steady-state pharmacokinetics of dolutegravir and by intrasubject comparison in the participants. This will be assessed with mean changes in the Area under the plasma concentration-time curve (AUC) before and after the administration of fluoxetine.

  Week 2 to the end of treatment at 12 weeks

• Mean changes in the Cmax of doultegravir

  The effect of chronic administration of dolutegravir on the steady-state pharmacokinetics of fluoxetine by intrasubject comparison in the participants. This will be assessed with mean changes in the Maximum plasma concentration (Cmax) before and after the administration of fluoxetine.

  Week 2 to the end of treatment at 12 weeks

• Mean changes in the Cmin of dolutegravir

  Description: The effect of chronic administration of fluoxetine on the steady-state pharmacokinetics of dolutegravir and by intrasubject comparison in the participants. This will be assessed with mean changes in the Minimum plasma concentration(Cmin) before and after the administration of fluoxetine.

  Week 2 to the end of treatment at 12 weeks

• Mean changes in the AUC of fluoxetine

  The effect of chronic administration of dolutegravir on the steady-state pharmacokinetics of fluoxetine by intrasubject comparison in the participants. This will be assessed with mean changes in the Area under the plasma concentration-time curve (AUC) before and after the administration of fluoxetine.

  Week 2 to the end of treatment at 12 weeks

• Mean changes in the Cmax of fluoxetine

  The effect of chronic administration of dolutegravir on the steady-state pharmacokinetics of fluoxetine by intrasubject comparison in the participants. This will be assessed with mean changes in the Maximum plasma concentration (Cmax) before and after the administration of fluoxetine

  Week 2 to the end of treatment at 12 weeks

• Mean changes in the Cmin of fluoxetine

  The effect of chronic administration of dolutegravir on the steady-state pharmacokinetics of fluoxetine by intrasubject comparison in the participants. This will be assessed with mean changes in the Minimum plasma concentration (Cmin) before and after the administration of fluoxetine.

  Week 2 to the end of treatment at 12 weeks

Secondary Outcomes (20)

• Proportion of participants reporting grade 3 or 4 Adverse Events as Assessed by the DAIDS AE Grading Table Corrected Version 2.1

  Baseline to weeks 2, 4, 8, and 12

• Proportion of participants with depression remission at week 12

  Baseline to the end of treatment at 12 weeks

• Proportion of participants with a change of greater than or equal to (≥) 50% in the depression score from baseline to weeks 6, 8, and 12

  Baseline to weeks 6, 8 and 12

• Proportion of participants that drop out (study dropouts) during the study

  Baseline to weeks 2, 4, 6, 8, and 12

• Proportion of participants with viral suppression (≤ 50 copies/mL)

  Baseline to the end of study at week 12

Study Arms (2)

Fluoxetine Arm

EXPERIMENTAL

Participants with a HAM-D score greater than 13 (moderate, moderately severe, and severe depression) will be recruited and allocated to the intervention group. The psychiatrist will commence the participants on fluoxetine (starting with 20mg daily). The psychiatrist will determine the dose of fluoxetine, and the dose may be adjusted during follow-up. Participants will receive Cognitive Behavioural Therapy (CBT) delivered by a Clinical psychologist in addition to fluoxetine as part of the standard routine care.

Drug: Fluoxetine; Behavioral: Cognitive-behavioral therapy

Cognitive Behavioural Therapy (CBT) Arm

ACTIVE COMPARATOR

Participants with HAM-D score between 8 and 13 (mild depression) will be recruited and allocated to the control group. They will receive only Cognitive Behavioural Therapy (CBT) as per standard routine care.

Behavioral: Cognitive-behavioral therapy

Interventions

Fluoxetine DRUG

Participants in the intervention arm will receive oral fluoxetine capsules starting with 20mg daily for 12 weeks. The dose of the fluoxetine may be adjusted during follow-up by titrating the dose against the participants' response..

Also known as: Prozac, Fluoxetine hydrochloride, Rapiflux, Sarafem, Selfemra, Fluoxetin, Lilly-110140, N-Methyl-gamma-(4-(trifluoromethyl)phenoxy)benzenepropanamine

Fluoxetine Arm

Cognitive-behavioral therapy BEHAVIORAL

Participants with HAM-D score of between 8 and 13 (mild depression) will receive sessions of Cognitive Behavioural Therapy (CBT) as per standard routine care. Participants in the intervention arm will also receive sessions of CBT as per standard routine care.

Also known as: Psychotherapy, Cognitive Behavioral Therapy, Cognitive Behavioural Therapy, Cognitive Psychotherapy, Cognitive Therapy, CBT

Cognitive Behavioural Therapy (CBT) Arm; Fluoxetine Arm

Eligibility Criteria

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

You may qualify if:

• Males and females aged 18 years and above
• Willing to provide informed consent.
• Confirmed HIV positive \[HIV-seropositive by Enzyme Linked Immunosorbent Assay (ELISA) and Western Blot assays\]
• Willingness to receive and or continue anti-HIV therapy (DTG-based cART) \& adhere to follow-up schedule
• Willing and able to comply with antidepressant medication(fluoxetine) regimen and scheduled follow-up visits
• Current depressive symptoms \[Subjects with depression (HAM-D-17 score ≥ 8)\]
• Adequate renal function (serum creatinine \< 1.5mg/dl)
• Adequate liver function \[aspartate aminotransferase (AST) and alanine transaminase (ALT) ≤1.5 x Upper Limits of Normal)

You may not qualify if:

• Current substance use disorder
• Imminent risk of suicide- Acute suicidal ideation, gestures, or attempts
• Presence of psychotic symptoms or known diagnosis of a primary psychotic disorder
• Presence of symptoms of bipolar disorder
• Currently taking antipsychotic medication
• Pregnant or willing to get pregnant or lactation
• Current or chronic medical condition that would likely preclude adherence to protocol or completion of the trial (per investigator judgment)
• Antidepressants, mood stabilisers or other neuroleptics intake within three months
• Use of drugs other than cART, especially known enzyme inducers or inhibitors
• Abnormal ECG (e.g., prolonged QT interval)
• History of intolerance to study drug (fluoxetine)

Sponsors & Collaborators

• University of Ibadan: lead
• Fogarty International Center of the National Institute of Health: collaborator
• State University of New York at Buffalo: collaborator
• Roswell Park Cancer Institute: collaborator
• College of Medicine University of Ibadan: collaborator
• University College Hospital, Ibadan, Nigeria: collaborator
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

University College Hospital

Ibadan, Oyo State, 200221, Nigeria

Location

Related Publications (16)

• Adedeji WA, Ma Q, Raji AM, Cha R, Rasaki OM, Hutson A, Taiwo BO, Charurat ME, Yusuf OB, Fehintola FA, Gureje O, Morse GD. Prevalence of depression among people living with HIV in rural hospitals in South-Western Nigeria-Association with clinico-demographic factors. AIDS Res Ther. 2023 Dec 16;20(1):89. doi: 10.1186/s12981-023-00586-0.

  PMID: 38104102 RESULT

• Borghetti A, Calcagno A, Lombardi F, Cusato J, Belmonti S, D'Avolio A, Ciccarelli N, La Monica S, Colafigli M, Delle Donne V, De Marco R, Tamburrini E, Visconti E, Di Perri G, De Luca A, Bonora S, Di Giambenedetto S. SLC22A2 variants and dolutegravir levels correlate with psychiatric symptoms in persons with HIV. J Antimicrob Chemother. 2019 Apr 1;74(4):1035-1043. doi: 10.1093/jac/dky508.

  PMID: 30561642 RESULT

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  PMID: 14639062 RESULT

• Reese MJ, Savina PM, Generaux GT, Tracey H, Humphreys JE, Kanaoka E, Webster LO, Harmon KA, Clarke JD, Polli JW. In vitro investigations into the roles of drug transporters and metabolizing enzymes in the disposition and drug interactions of dolutegravir, a HIV integrase inhibitor. Drug Metab Dispos. 2013 Feb;41(2):353-61. doi: 10.1124/dmd.112.048918. Epub 2012 Nov 6.

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  PMID: 28915895 RESULT

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  PMID: 27984559 RESULT

• Eshun-Wilson I, Siegfried N, Akena DH, Stein DJ, Obuku EA, Joska JA. Antidepressants for depression in adults with HIV infection. Cochrane Database Syst Rev. 2018 Jan 22;1(1):CD008525. doi: 10.1002/14651858.CD008525.pub3.

  PMID: 29355886 RESULT

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  PMID: 28900756 RESULT

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  PMID: 28577548 RESULT

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MeSH Terms

Conditions

Depression; Depressive Disorder, Major

Interventions

Fluoxetine; Cognitive Behavioral Therapy; Psychotherapy

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Behavior Therapy; Behavioral Disciplines and Activities

Study Officials

• Waheed A Adedeji

  College of Medicine, University of Ibadan, Nigeria

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Waheed A Adedeji

CONTACT

+2348038433259; wad_deji@yahoo.com

Fatai A Fehintola

CONTACT

fentolamine@yahoo.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lecturer

Study Record Dates

• First Submitted: May 15, 2025
• First Posted: August 8, 2025
• Study Start: August 14, 2025
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): March 31, 2028
• Last Updated: August 8, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: After the study
• Access Criteria: Researchers can access individual participant data by submitting a proposal and data sharing agreement to the principal investigator.

Locations

NG (1)