Novolin R (recombinant human insulin) / Novo Nordisk - LARVOL DELTA

INI-CSF: Measurement of Insulin Levels in Cerebral Spinal Fluid (CSF) of Healthy Adults After a Single Intranasal Dose (clinicaltrials.gov) - P1 | N=2 | Terminated | Sponsor: HealthPartners Institute | We are no longer able to obtain the intranasal delivery device. We do not have adequate funding available to continue with an alternative intranasal delivery device.

Enrollment change • Trial termination

Acute Effect of Intranasal Insulin on Food Intake Among Middle-Aged African American Adults: The FIINAAL Study. (PubMed, J Endocr Soc) - "A total of 39 participants received intranasal doses of Novolin-R (40 IU) and a saline placebo on separate days in a double-blind, counterbalanced, crossover design, with 3-day, eucaloric, nutritionally balanced diets preceding each dose...Acute intranasal insulin was associated with a reduced desire for sweet foods and with increased feelings of fullness, but not reduced food intake, among middle-aged African American adults. Eating behavior and appetite changes should be explored further as possible side effects of intranasal insulin treatment for cognitive decline in diverse populations."

Journal • Alzheimer's Disease • CNS Disorders • Obesity

Pyruvate dehydrogenase kinase 4 inhibition or deletion in alpha cells enhances glucagon secretion at low glucose in mouse and human islets and improves glucose tolerance in diet-induced obese male mice (EASD 2025) - "For ITT, due to sex-specific differences in insulin sensitivity, females received 0.7 U/kg and males 0.85 U/kg insulin (Actrapid)... These results demonstrate that deletion or inhibition of PDK4 in α-cells improves glucagon secretion in response to low glucose (G1) in vitro in mouse and human islets. This echoes the reduced in vivo hypoglycemic excursion in response to insulin in CTL diet mice. In addition, α-cell PDK4 deletion improves glucose tolerance in diet-induced obese male mice."

Preclinical • Diabetes • Metabolic Disorders • Obesity • PDK4

INI-CSF-MA: Measurement of Insulin Levels in the Cerebrospinal Fluid of Healthy Adults After a Single Intranasal Dose - Middle Age (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: HealthPartners Institute | N=18 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal

ITA: Intranasal Insulin for Treatment of Alcohol Use Disorder (clinicaltrials.gov) - P1/2 | N=40 | Recruiting | Sponsor: Brown University | Trial completion date: Mar 2025 ➔ Jan 2027 | Trial primary completion date: Mar 2025 ➔ Dec 2026

Trial completion date • Trial primary completion date • Addiction (Opioid and Alcohol)

Human Models of Selective Insulin Resistance: Pancreatic Clamp (clinicaltrials.gov) - P1 | N=36 | Not yet recruiting | Sponsor: Columbia University | Initiation date: Jun 2025 ➔ Jan 2026

Trial initiation date • Genetic Disorders • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity

Effect of Intraperitoneal Insulin Administration After Laparoscopy in Insulin-Resistant Patients on Prevention of Postoperative Adhesion Recurrence: A Randomized Controlled Trial (clinicaltrials.gov) - P=N/A | N=100 | Not yet recruiting | Sponsor: Ain Shams University

New trial

INI-CSF-MA: Measurement of Insulin Levels in the Cerebrospinal Fluid of Healthy Adults After a Single Intranasal Dose - Middle Age (clinicaltrials.gov) - P1 | N=18 | Not yet recruiting | Sponsor: HealthPartners Institute | Initiation date: Mar 2025 ➔ Jun 2025

Trial initiation date

Effects of Intranasal Insulin on Neuroimaging Markers and Cognition in Patients With Psychotic Disorders (clinicaltrials.gov) - P2 | N=87 | Completed | Sponsor: Mclean Hospital | Recruiting ➔ Completed

Trial completion • Bipolar Disorder • CNS Disorders • Mood Disorders • Psychiatry • Schizophrenia

INI-PD: Intranasal Insulin in Parkinson's Disease (clinicaltrials.gov) - P2 | N=31 | Completed | Sponsor: HealthPartners Institute | Active, not recruiting ➔ Completed | Trial completion date: Feb 2025 ➔ Aug 2024

Trial completion • Trial completion date • CNS Disorders • Movement Disorders • Parkinson's Disease

Safety and Tolerability of Intranasal Insulin in Parkinson's Disease (AAN 2025) - "Subjects received intranasal treatment for 21 days with normal saline, 20, 40, or 80 IU of Novolin R. Safety and tolerability were assessed by measuring hypoglycemia, weight, and adverse events...IN insulin exhibits an acceptable safety profile in patients with PD. This is one of the first explorations into safety of IN insulin in PD. Further testing is warranted to determine whether it is efficacious in reducing motor and cognitive symptoms in this population."

Clinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Diabetes • Hypoglycemia • Metabolic Disorders • Movement Disorders • Parkinson's Disease

Comparison of Thrice-Daily Premixed Human Insulin with Basal-Bolus Therapy Among Patients with Poorly Controlled Type 2 Diabetes Mellitus (clinicaltrials.gov) - P4 | N=44 | Completed | Sponsor: Hospital Sultanah Aminah Johor Bahru

New P4 trial • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Various Procedural Treatment Options for Post-acne Atrophic Scars (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: Sheikh Zayed Medical College

New P2 trial • Acne Vulgaris

Human Models of Selective Insulin Resistance: Pancreatic Clamp (clinicaltrials.gov) - P1 | N=36 | Not yet recruiting | Sponsor: Columbia University | Trial completion date: Feb 2027 ➔ Feb 2028 | Initiation date: Dec 2024 ➔ Jun 2025 | Trial primary completion date: Dec 2026 ➔ Dec 2027

Trial completion date • Trial initiation date • Trial primary completion date • Genetic Disorders • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity

INI-PD: Intranasal Insulin in Parkinson's Disease (clinicaltrials.gov) - P2 | N=30 | Active, not recruiting | Sponsor: HealthPartners Institute | Trial completion date: Nov 2024 ➔ Feb 2025

Trial completion date • CNS Disorders • Movement Disorders • Parkinson's Disease

LEV PS: Dose Response Study of Transdermal Human Insulin in Patients (clinicaltrials.gov) - P2/3 | N=30 | Not yet recruiting | Sponsor: Transdermal Delivery Solutions Corp | Trial completion date: Feb 2025 ➔ Dec 2025 | Trial primary completion date: Dec 2024 ➔ Oct 2025

Trial completion date • Trial primary completion date • Diabetes • Metabolic Disorders

INI-CSF-MA: Measurement of Insulin Levels in the Cerebrospinal Fluid of Healthy Adults After a Single Intranasal Dose - Middle Age (clinicaltrials.gov) - P1 | N=18 | Not yet recruiting | Sponsor: HealthPartners Institute | Initiation date: Oct 2024 ➔ Feb 2025

Trial initiation date

INI-PD: Intranasal Insulin in Parkinson's Disease (clinicaltrials.gov) - P2 | N=30 | Active, not recruiting | Sponsor: HealthPartners Institute | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Movement Disorders • Parkinson's Disease

INI-CSF: Measurement of Insulin Levels in Cerebral Spinal Fluid (CSF) of Healthy Adults After a Single Intranasal Dose (clinicaltrials.gov) - P1 | N=12 | Suspended | Sponsor: HealthPartners Institute | Recruiting ➔ Suspended

Trial suspension

Human Models of Selective Insulin Resistance: Pancreatic Clamp (clinicaltrials.gov) - P1 | N=36 | Not yet recruiting | Sponsor: Columbia University | Initiation date: Sep 2024 ➔ Dec 2024 | Trial primary completion date: Aug 2026 ➔ Dec 2026

Trial initiation date • Trial primary completion date • Genetic Disorders • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity

INI-CSF: Measurement of Insulin Levels in Cerebral Spinal Fluid (CSF) of Healthy Adults After a Single Intranasal Dose (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: HealthPartners Institute | Trial completion date: Nov 2024 ➔ Nov 2025 | Trial primary completion date: Aug 2024 ➔ Aug 2025

Trial completion date • Trial primary completion date

Human Models of Selective Insulin Resistance: Pancreatic Clamp (clinicaltrials.gov) - P1 | N=36 | Not yet recruiting | Sponsor: Columbia University

New P1 trial • Genetic Disorders • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity

INI-PD: Intranasal Insulin in Parkinson's Disease (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: HealthPartners Institute | Trial completion date: Jul 2024 ➔ Oct 2024 | Trial primary completion date: Jun 2024 ➔ Sep 2024

Trial completion date • Trial primary completion date • CNS Disorders • Movement Disorders • Parkinson's Disease

Dexamethasone/Pancreatic Clamp P&F (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: Columbia University | N=16 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Genetic Disorders • Hepatology • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity

Assessment of subcutaneously administered insulins using in vitro release cartridge: Medium composition and albumin binding. (PubMed, Int J Pharm) - "Drug disappearance was assessed for solution, suspension and in situ precipitating insulin products (Actrapid, Levemir, Tresiba, Mixtard 30, Insulatard, Lantus) using the flow-based cartridge. Albumin-binding acylated insulin analogs exhibited rapid disappearance from the cartridge; however, sustained retention was achieved by coupling albumin to the matrix. An in vitro-in vivorelation was established for the non-albumin-binding insulins.The IVR cartridge is flexible with potential in formulation development as shown by the ability to accommodate solutions, suspensions, and in situ forming formulations while tailoring of the system to probe in vivo relevant medium effects and tissue constituent interactions."

Journal • Preclinical