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Diabetic Macular EdemaPhase 2NCT03161652

Effect of Levosulpiride on Retinal Alterations in Patients With Diabetic Retinopathy and Diabetic Macular Edema

A Phase 2 study testing DME lactose pill, DME levosulpiride and DR lactose pill in people with Diabetic Macular Edema and Diabetic Retinopathy, run by Carmen Clapp at 2 sites in Mexico.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

This is a randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of levosulpiride to improve retinal alterations due to diabetic macular edema and diabetic retinopathy Read more about this study

Who is it for?
Ages 40 to 69 years
Conditions the study is for
Diabetic Macular Edema, Diabetic Retinopathy
What is being tested?
DME lactose pill, DME levosulpiride and DR lactose pill
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
120 participants
Where
2 sitesMexico
Study dates
24 May 2017to Jun 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 40 to 69 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age equal or greater than 40 years but no older than 69 years
  • Male and female subjects with mild and moderate diabetic macular edema (DME), non-proliferative diabetic retinopathy (DR), and with proliferative DR undergoing medically prescribed vitrectomy.
  • Signing informed consent
  • Without ocular complications: severe myopia (> 6 diopters), ocular media opacity, retinal detachment, etc.
  • Without previous ocular treatments: ocular surgeries, retinal laser photocoagulation, intravitreal administration of antiangiogenic agents (delivered < 6 months before enrollment).
  • Prolactin serum levels ≤ 20 ng/ml
Show all 10Show fewer
  • With normal or mild loss of kidney function (glomerular filtration rate >60 ml/min) for groups with DME and DR without vitrectomy.
  • With mild to severe loss of kidney function (glomerular filtration rate >30 ml/min) for groups with DR undergoing vitrectomy.
  • Without contraindications for the use of levosulpiride (Parkinson disease, epilepsy, breast cancer, alcoholism, hypokalemia).
  • Without hyperprolactinemia inducing conditions: Pathologies (hypothyrodism, hepatic dysfunction, prolactinomas); Medication (antipsychotics, antidepressants, prokinetics, other)

Who cannot join

  • Not meeting inclusion criteria.
  • Adverse and intolerable drug effects.
  • Not complying with study medication
  • Inability to continue in-hospital appointments.
  • Missing outcome data
  • Hesitation to continue with study medication
  • Relocation to another state or country
  • Voluntary withdrawal of consent

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Carmen Clapp, Ph.D. contact

52442 2381028

clapp@unam.mx

Ludivina Robles Osorio, M.D., Ph.D. contact

52442 1921200 ext. 5301

ludirobles7@yahoo.com

Mexico2 sites, 2 recruiting

  • Instituto Mexicano de Oftalmologia (IMO)

    Querétaro City, Querétaro, 76090

    Ellery Lopez Star, M.D., 52442 229 0776 ext. 118, ellerylopezstar@gmail.com

    Marlon R García Roa, M.D., 52442 229 0776, drmgroa@hotmail.com

    Recruiting

  • Instituto de la Retina del Bajio SC (INDEREB)

    Querétaro City, Querétaro, 76187

    Renata Garcia Franco, M.D., 52442 3407952, renatagarciafranco@gmail.com

    Carlos D Nuñez Amaro, M.Sc., 52442 3961722, qbpcarlosamaro@gmail.com

    Recruiting

Other trials in Mexico

About this study

Official title: Clinical Trial to Evaluate the Safety and Efficacy of Levosulpiride to Improve Retinal Alterations in Patients With Diabetic Retinopathy and Diabetic Macular Edema.

This is a randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of levosulpiride to improve retinal alterations due to diabetic macular edema and diabetic retinopathy

Read the detailed description

Diabetic retinopathy (DR) and diabetic macular edema (DME) are the primary cause of irreversible blindness and visual impairment in working-age adults. Nearly 80% of patients with diabetes will experience some degree of DR and DME 15-20 years after diagnosis. Altered blood parameters (glucose, lipids, and pressure) influence disease development and progression; however, the combined values of these parameters account for only 10% of the risk of DR. Laser therapy is effective for preserving sight but is poor for reversing visual loss. Anti-angiogenic therapies are effective and less destructive but require frequent intravitreal delivery, which raises the risk of infection and ocular complications. Therefore, the prevention and treatment of DR and DME should include other modifiable factors. Data from preclinical studies support a protective role for the serum levels of the hormone prolactin. The trial investigates a new specific therapy for DR and DME based on elevating the circulating levels of prolactin with the prokynetic, dopamine D2 receptor blocker, levosulpiride. It is a prospective, randomized clinical study in patients with DR and DME in which ophthalmologic and health parameters evaluated before and after starting the study medication will determine the efficacy and safety of treatment.

Patient registries: Patients are enrolled at the time of a routine health care service. The caregiver and patient together, in a standardized uniform manner for every patient, will collect the data. Data collection procedures are clearly described and include protocols, policies, and the formatted listing of all the data elements, their full definitions and validation rules. All personnel involved in data collection are qualified registry trained. The same physicians, laboratory technicians, and graduate students will evaluate and collect the data from all patients. An individual fully knowledgeable of all protocols, policies, procedures, and definitions in the registry will be designated as Accountable for Data Quality. This individual (coordinator) should ensure that all collected data are complete, accurate, and valid. Data logically inconsistent will be confronted to information in external database. Data collected on formatted paper forms are entered into a computer and electronic registries carefully reviewed by a third party to identify missing data, invalid or erroneous entries, and inconsistent data. Any data review activity and remediation efforts will be documented. Amelioration of data problems may include querying the personnel uploading the data, the coordinator, the interviewer, or the patient. The proposed sample size and study duration are the minimum required and are based on biological models of DR and on clinical experience evaluating primary data associated with the study. These parameters may have to be modified to accommodate the sample size required to obtain clinically important differences and their statistical evaluation, access to eligible patients, lack of adherence to therapy at specific calendar dates (holidays), etc. Statistical methods include those evaluating continuous and categorical variables, incidence and prevalence, the association between a risk factor and outcome, and the relative contribution of confounding factors.

Being tested
DME lactose pill, DME levosulpiride, DR lactose pill, DR levosulpiride, DR vitrectomy lactose pill
Keywords
diabetic retinopathy, blindness, eye, macular edema, prolactin, dopamine antagonists, peptide hormones
Medical subject headings
Diabetic Retinopathy, Blindness, Macular Edema

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DME lactose pillDrug

    Also called placebo, sugar

    Patients with DME will take placebo orally 3 times a day (TID) for 8 weeks.The placebo is taken on top of standard therapy for diabetes and blood pressure control.

  • DME levosulpirideDrug

    Also called dopamine D2 receptor blocker

    Patients with DME will take levosulpiride (75 mg/day) orally TID for 8 weeks. Levosulpiride is taken on top of standard therapy for diabetes and blood pressure control.

  • DR lactose pillDrug

    Also called placebo, sugar

    Patients with non-proliferative DR will take a lactose pill (placebo) orally TID for 8 weeks. The placebo is taken on top of standard therapy for diabetes and blood pressure control.

  • DR levosulpirideDrug

    Also called dopamine D2 receptor blocker

    Patients with non-proliferative DR will take levosulpiride (75 mg/day) orally TIDfor 8 weeks. Levosulpiride is taken on top of standard therapy for diabetes and blood pressure control.

  • DR vitrectomy lactose pillDrug

    Also called placebo, sugar

    Patients with proliferative DR (undergoing medically prescribed vitrectomy 7 days after starting the study medication) will have to take a lactose pill (placebo) orally TID for one week. The last placebo pill will be taken on the morning of the day vitrectomy is performed. The placebo is taken on top of standard therapy for diabetes and blood pressure control.

  • DR vitrectomy levosulpirideDrug

    Also called dopamine D2 receptor blocker

    Patients with proliferative DR (undergoing medically prescribed vitrectomy 7 days after starting the study medication) will take levosulpiride (75 mg/day) orally TID for one week. The last pill will be taken on the morning of the day vitrectomy is performed. Levosulpiride is taken on top of standard therapy for diabetes and blood pressure control.

  • DME plus ranibizumab lactose pillDrug

    Also called placebo, sugar

    Patients with DME with conventional intravitreal antiangiogenic therapy with ranibizumab (0.5 mg every 4 weeks for 12 weeks) will take a lactose pill (placebo) orally TID for 24 weeks. The placebo is taken on top of standard therapy for diabetes and blood pressure control.

  • DME plus ranibizumab levosulpirideDrug

    Also called dopamine D2 receptor blocker

    Patients with DME with receive intravitreal antiangiogenic therapy with ranibizumab (0.5 mg every 4 weeks for 12 weeks) will take a levosulpiride (75 mg/day) orally TID for 24 weeks. The study medication is taken on top of standard therapy for diabetes and blood pressure control.

Study groups in NCT03161652
Study groupRoleWhat they receive
DME lactose pillPlacebo comparatorPatients with DME will be randomized to take a lactose pill (placebo).
Receives: Drug: DME lactose pill
DME levosulpirideExperimentalPatients with DME will be randomized to take levosulpiride.
Receives: Drug: DME levosulpiride
DR lactose pillPlacebo comparatorPatients with non-proliferative DR will be randomized to take a lactose pill (placebo)
Receives: Drug: DR lactose pill
DR levosulpirideExperimentalPatients with non-proliferative DR will be randomized to take levosulpiride
Receives: Drug: DR levosulpiride
DR, vitrectomy lactose pillPlacebo comparatorPatients with proliferative DR (undergoing medically prescribed vitrectomy 7 days after starting the study) will be randomized to take a lactose pill (placebo).
Receives: Drug: DR vitrectomy lactose pill
DR, vitrectomy levosulpirideExperimentalPatients with proliferative DR (undergoing medically prescribed vitrectomy 7 days after starting the study) will be randomized to take levosulpiride.
Receives: Drug: DR vitrectomy levosulpiride
DME plus ranibizumab lactose pillPlacebo comparatorPatients with DME that will receive intravitreal antiangiogenic therapy with ranibizumab will be randomized to take a lactose pill (placebo)
Receives: Drug: DME plus ranibizumab lactose pill
DME plus ranibizumab levosulpirideExperimentalPatients with DME that will receive intravitreal antiangiogenic therapy with ranibizumab will be randomized to take levosulpiride
Receives: Drug: DME plus ranibizumab levosulpiride

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Visual acuity

    Number of letters recognized in the Early Treatment Diabetic Retinopathy Study (ETDRS) chart test after correcting for any refractive error (myopia, hyperopia, or astigmatism)

    Measured: 5 minutes

  2. Retinal thickness

    Retinal thickness is evaluated by non-invasive optical coherence tomography (OCT) imaging via qualitative and quantitative analyses. For qualitative analyses, OCT images approaching the histological level of retinal morphology are interpreted based on normal and diseased features (hyper-reflective or hypo-reflective lesions, shadowing, and anatomical changes). Quantitative analysis evaluates retinal reflective signals and their correlation with retinal morphology by computer image-processing algorithms (retinal thickness map, volume, area, 1, 3, and 6 mm ETDRS circle diameters).

    Measured: Pupils are dilated (eye drops) for 10 to 15 minutes and optical coherence tomography (OCT) images recorded during 5 minutes.

  3. Retinal hard exudates and hemorrhages

    Number, size, and location of retinal hard exudates and hemorrhages evaluated by indirect ophthalmoscopy

    Measured: Pupils are dilated (eye drops) for 10 to 15 minutes and fundus images recorded during 5 minutes

  4. Retinal microaneurisms, leakage area, cotton-wool spots, venous beading, microvascular and vascular abnormalities

    Location, intensity, and source of above alterations evaluated by fundus fluorescein angiography imaging qualitative and quantitative analysis of hyper-fluorescent or hypo-fluorescent regions.

    Measured: Pupils are dilated (eye drops) for 10 to 15 minutes and fundus images recorded before and at different times (0.5 to 5 minutes) after fluorescein injection.

  5. Prolactin serum levels

    ng/ml levels of prolactin quantified in serum samples using the IMMULITE 2000 XPi immunoassay system

    Measured: 1-2 minutes (duration of blood withdrawal)

  6. Prolactin vitreous levels

    ng/ml levels of prolactin quantified in vitreous samples using the IMMULITE 2000 XPi immunoassay system

    Measured: 2 minutes (duration of vitreous withdrawal during medically prescribed vitrectomy)

  7. Vasoinhibin vitreous levels

    Optical density values of vasoinhibins obtained by the immunoprecipitation-Western blot analysis of vitreous samples

    Measured: 2 minutes (duration of vitreous withdrawal during medically prescribed vitrectomy)

Secondary outcomes (3)

  1. Pyruvic glutamic transaminase (TGP) and thyroid stimulating hormone (TSH) serum levels

    U/L (TGP) and uU/mL (TSH) quantified in serum samples by the Bioclin Kinetic Transaminase ALT (TGP) Kit and the automatic quimioluminescent evaluator (TSH)

    Measured: 1-2 minutes (duration of blood withdrawal)

  2. Blood glycated hemoglobin and creatinine serum levels

    Glycated hemoglobin (evaluated by boronate affinity chromatography) and creatinine (evaluated by the Jaffe reaction) levels are expressed as % and mg/dL, respectively.

    Measured: 1-2 minutes (duration of blood withdrawal)

  3. Blood pressure

    Systolic and diastolic values in mmHg

    Measured: 5 minutes

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 May 2017
  2. Study start24 May 2017
  3. Primary completionDec 2026 (estimated)
  4. Study completionJun 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
The study investigates a medication causing hyperprolactinemia (levosulpiride) to treat diabetic retinopathy (DR) and diabetic macular edema (DME). Subjects are from four different populations, those with DME, non-proliferative DR, those undergoing vitrectomy due to proliferative DR, and those with DME plus standard intravitreal antiangiogenic therapy with ranibizumab. Immediately after baseline, each of the four groups are randomly split into two subgroups: one receiving placebo (sugar pill) and the other levosulpiride. Ophthalmologic and health outcomes between groups 1 and 2 (DME: placebo and levosulpiride), 3 and 4 (DR: placebo and levosulpiride), and 7 and 8 (DME plus ranibizumab: placebo and levosulpiride) evaluate the efficacy and safety of the study medication. Comparison of serum and vitreous prolactin levels between the groups undergoing vitrectomy (DR: placebo and levosulpiride) serve as a proof of principle that prolactin enters the eye to counteract disease progression.
Masking
Triple blind
Who is masked
Participant, Care provider, Outcomes assessor
Enrolment
120 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03161652
Sponsor's protocol ID
LDRDME_247164
Status last verified
Nov 2025
First submitted
18 May 2017
Last updated
18 Nov 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided: It is yet undecided whether case reports will be published in medical journals throughout the course of the study. No identifier linking participants in the study to research records will be made public or reported.

Publications

  • Aranda J, Rivera JC, Jeziorski MC, Riesgo-Escovar J, Nava G, Lopez-Barrera F, Quiroz-Mercado H, Berger P, Martinez de la Escalera G, Clapp C. Prolactins are natural inhibitors of angiogenesis in the retina. Invest Ophthalmol Vis Sci. 2005 Aug;46(8):2947-53. doi: 10.1167/iovs.05-0173.

    PubMed 16043870

  • Garcia C, Aranda J, Arnold E, Thebault S, Macotela Y, Lopez-Casillas F, Mendoza V, Quiroz-Mercado H, Hernandez-Montiel HL, Lin SH, de la Escalera GM, Clapp C. Vasoinhibins prevent retinal vasopermeability associated with diabetic retinopathy in rats via protein phosphatase 2A-dependent eNOS inactivation. J Clin Invest. 2008 Jun;118(6):2291-300. doi: 10.1172/JCI34508.

    PubMed 18497878

  • Clapp C, Thebault S, Arnold E, Garcia C, Rivera JC, de la Escalera GM. Vasoinhibins: novel inhibitors of ocular angiogenesis. Am J Physiol Endocrinol Metab. 2008 Oct;295(4):E772-8. doi: 10.1152/ajpendo.90358.2008. Epub 2008 Jun 10.

    PubMed 18544641

  • Arnold E, Rivera JC, Thebault S, Moreno-Paramo D, Quiroz-Mercado H, Quintanar-Stephano A, Binart N, Martinez de la Escalera G, Clapp C. High levels of serum prolactin protect against diabetic retinopathy by increasing ocular vasoinhibins. Diabetes. 2010 Dec;59(12):3192-7. doi: 10.2337/db10-0873. Epub 2010 Sep 7.

    PubMed 20823101

  • Triebel J, Macotela Y, de la Escalera GM, Clapp C. Prolactin and vasoinhibins: Endogenous players in diabetic retinopathy. IUBMB Life. 2011 Oct;63(10):806-10. doi: 10.1002/iub.518. Epub 2011 Sep 13.

    PubMed 21913303

  • Ramirez M, Wu Z, Moreno-Carranza B, Jeziorski MC, Arnold E, Diaz-Lezama N, Martinez de la Escalera G, Colosi P, Clapp C. Vasoinhibin gene transfer by adenoassociated virus type 2 protects against VEGF- and diabetes-induced retinal vasopermeability. Invest Ophthalmol Vis Sci. 2011 Nov 21;52(12):8944-50. doi: 10.1167/iovs.11-8190.

    PubMed 22003113

  • Arnold E, Thebault S, Baeza-Cruz G, Arredondo Zamarripa D, Adan N, Quintanar-Stephano A, Condes-Lara M, Rojas-Piloni G, Binart N, Martinez de la Escalera G, Clapp C. The hormone prolactin is a novel, endogenous trophic factor able to regulate reactive glia and to limit retinal degeneration. J Neurosci. 2014 Jan 29;34(5):1868-78. doi: 10.1523/JNEUROSCI.2452-13.2014.

    PubMed 24478366

  • Arredondo Zamarripa D, Diaz-Lezama N, Melendez Garcia R, Chavez Balderas J, Adan N, Ledesma-Colunga MG, Arnold E, Clapp C, Thebault S. Vasoinhibins regulate the inner and outer blood-retinal barrier and limit retinal oxidative stress. Front Cell Neurosci. 2014 Oct 20;8:333. doi: 10.3389/fncel.2014.00333. eCollection 2014.

    PubMed 25368550

  • Diaz-Lezama N, Wu Z, Adan-Castro E, Arnold E, Vazquez-Membrillo M, Arredondo-Zamarripa D, Ledesma-Colunga MG, Moreno-Carranza B, Martinez de la Escalera G, Colosi P, Clapp C. Diabetes enhances the efficacy of AAV2 vectors in the retina: therapeutic effect of AAV2 encoding vasoinhibin and soluble VEGF receptor 1. Lab Invest. 2016 Mar;96(3):283-95. doi: 10.1038/labinvest.2015.135. Epub 2015 Nov 16.

    PubMed 26568297

  • Melendez Garcia R, Arredondo Zamarripa D, Arnold E, Ruiz-Herrera X, Noguez Imm R, Baeza Cruz G, Adan N, Binart N, Riesgo-Escovar J, Goffin V, Ordaz B, Pena-Ortega F, Martinez-Torres A, Clapp C, Thebault S. Prolactin protects retinal pigment epithelium by inhibiting sirtuin 2-dependent cell death. EBioMedicine. 2016 May;7:35-49. doi: 10.1016/j.ebiom.2016.03.048. Epub 2016 Apr 20.

    PubMed 27322457

  • Robles-Osorio ML, Garcia-Franco R, Nunez-Amaro CD, Mira-Lorenzo X, Ramirez-Neria P, Hernandez W, Lopez-Star E, Bertsch T, Martinez de la Escalera G, Triebel J, Clapp C. Basis and Design of a Randomized Clinical Trial to Evaluate the Effect of Levosulpiride on Retinal Alterations in Patients With Diabetic Retinopathy and Diabetic Macular Edema. Front Endocrinol (Lausanne). 2018 May 29;9:242. doi: 10.3389/fendo.2018.00242. eCollection 2018.

    PubMed 29896154

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing DME lactose pill, DME levosulpiride and DR lactose pill in people with Diabetic Macular Edema and Diabetic Retinopathy, run by Carmen Clapp at 2 sites in Mexico.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 18 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Mexico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Carmen Clapp, Ph.D. (52442 2381028, clapp@unam.mx), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Visual acuity (time frame: 5 minutes). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03161652, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2025.

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