Cerebral Blood FlowPhase 1/2NCT06682767
A Nutritional and Pharmacological Intervention for Body, Brain, and Longevity Effects (NIBBLE)
A Phase 1/2 study testing FMD1 (LNT22-017-1) and Rapamycin in people with Cerebral Blood Flow and APOE 4, run by Cedars-Sinai Medical Center at 1 site in United States.
Trial summary
The study aims to evaluate the safety, feasibility, and preliminary efficacy of the fasting-mimicking diet (FMD) or low-dose daily rapamycin treatment relative to a matched placebo control group when administered over 8 weeks in middle-aged adults at elevated risk for Alzheimer's disease due to the apolipoprotein… Read more about this study
- Who is it for?
- Ages 45 to 65 years
- Conditions the study is for
- Cerebral Blood Flow, APOE 4
- What is being tested?
- FMD1 (LNT22-017-1) and Rapamycin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2026to Jun 2028
- Phase
- Phase 1/2
- 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 45 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of signed and dated informed consent form
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Male or female, aged 45-65 years at screening
- Carrier of at least one copy of the APOE e4 allele
- BMI 20-39kg/m2 (inclusive) at screening
- On a stable medication regimen for at least 3 months.
- For females: Post-menopausal status or use of highly effective contraception.
Who cannot join
- Has any medical disease or condition that, in the opinion of the principal investigator (PI) or appropriate study personnel, precludes study participation* (*Including acute, subacute, intermittent or chronic medical disease or condition that would place the subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the subject's successful completion of this trial);
- Significant depression (PHQ-9>9) or generalized anxiety (GAD-7>9)
- Diagnosis of a significant neurological condition such as multiple sclerosis, epilepsy, Parkinson's disease, major stroke
- Contraindications to MRI such as claustrophobia, cardiac pacemaker, etc.
- Current adherence or adherence within the past 3 months to a specialized diet (e.g. ketogenic, paleo, intermittent fasting, raw food, vegan)
- Food allergies (e.g. dairy, eggs, fish/shellfish, peanuts, tree nuts, soy, wheat, sesame, corn)
Show all 25Show fewer
- Diagnosis of mild cognitive impairment or dementia; use of an FDA-approved medication for Alzheimer's disease; MoCA<23
- Diabetes (hbA1c >6.5%) or anti-diabetic medications
- History of gastric bypass;
- Inflammatory bowel disease
- Small or large bowel resection
- Subjects with recent weight loss (>5%), use of weight loss medication, participated in a weight loss program in the past 3 months
- Use of immune suppression drugs;
- Contraindication for study foods (special food needs and allergy);
- Women who are pregnant, lactating, or trying to conceive
- Women who are on hormone replacement therapy
- Alcohol dependency (alcohol intake greater than two drinks per day for women and three drinks per day for men)
- Current smoker or tobacco use within 3 months.
- Active malignant cancer or history of malignancy within the last 1 yea1s (except non-melanoma skin cancer)
- Serious psychiatric disorders such as schizophrenia, bipolar disorder, eating disorders
- Persons with allergy to animal dander or animal-instigated asthma
- Required use of drugs that affect cytochrome P450 3A4 or alter cerebral blood flow (see Appendix 1 for tables of excluded medications)
- Current or chronic liver, kidney, cardiac, or pulmonary diseases
- Untreated hypertriglyceridemia (fasting triglycerides > 300 mg/dl)
- Poorly controlled blood pressure (systolic BP > 160 or diastolic BP > 100 mmHg
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Cedars Sinai Medical Center
Los Angeles, California, 90048
Mitzi Gonzales, PhD, 424-315-0228, mitzi.gonzales@cshs.org
Sara Espinoza, MD, sara.espinoza@cshs.org
About this study
Official title: A Nutritional and Pharmacological Intervention for Body, Brain, and Longevity Effects (NIBBLE) - A Randomized Open-label Intervention of the Fasting-mimicking Diet (FMD) and Rapamycin (NIBBLE)
The study aims to evaluate the safety, feasibility, and preliminary efficacy of the fasting-mimicking diet (FMD) or low-dose daily rapamycin treatment relative to a matched placebo control group when administered over 8 weeks in middle-aged adults at elevated risk for Alzheimer's disease due to the apolipoprotein (APOE) ε4 allele. Participants randomly assigned to the FMD intervention will adhere to FMD for 5-days over three cycles for a period of approximately 8 weeks. Participants randomly assigned to the rapamycin and placebo groups will take 1 mg of rapamycin or a matched placebo pill daily for approximately 8 weeks.
Read the detailed description
Participants assigned to the FMD arm will adhere to the diet for 5 days over three cycles for a period of 8 weeks. The FMD diet is produced by L-Nutra and provides 1100 kcals on day 1 and 800 kcals on days 2-5. The diet consists of ingredients which are Generally Regarded As Safe (GRAS) selected for their fasting mimicking properties. Participants randomized to the rapamycin group will receive 1 mg rapamycin daily for 8 weeks and those in the placebo arm will take one matched placebo pill daily for 8 weeks.
- Conditions
- Cerebral Blood Flow, APOE 4
- Being tested
- FMD1 (LNT22-017-1), Rapamycin, Placebo
- Keywords
- APOE 4, prevention, nutritition, fasting mimicking diet, diet, Alzheimer's disease, rapamycin
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FMD1 (LNT22-017-1)Dietary supplement
FMD is a plant-based ketogenic diet that provides essential nutrients while maintaining hypo-caloric content. FMD is administered cyclically with 3-5 consecutive days of the diet followed by resumption of normal eating.
RapamycinDrug
Participants randomly assigned to the rapamycin arm will take 1 mg of rapamycin daily for approximately 8 weeks..
PlaceboDrug
Participants randomly assigned to the placebo arm will take one placebo pill daily for approximately 8 weeks.
| Study group | Role | What they receive |
|---|---|---|
| FMD - Intervention | Experimental | Participants in the FMD group will be asked to refrain from consuming any calorie-containing foods or drinks other than the provided study foods/drinks during the designated intervention days each month. Receives: Dietary Supplement: FMD1 (LNT22-017-1) |
| Rapamycin | Experimental | Participants randomly assigned to the rapamycin arm will take 1 mg of rapamycin daily for approximately 8 weeks. Receives: Drug: Rapamycin |
| Placebo | Placebo comparator | Participants randomly assigned to the placebo arm will take one placebo pill daily for approximately 8 weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate and compare the safety of an approximately 8-week FMD or low dose rapamycin intervention relative to a matched control group
Endpoint: Number of adverse events in the intervention groups relative to the placebo group.
Measured: From pre- to post-treatment (Day 72 +/- 5 days)
Secondary outcomes (2)
Investigate the effect of an approximately 8-week FMD or low dose rapamycin intervention relative to a matched control group.
Endpoint: Cerebral blood flow - Cerebral blood flow will be assessed through brain magnetic resonance imaging arterial spin labeling sequence.
Measured: From pre- to post-treatment (Day 72 +/- 5 days)
Investigate and compare the impact of the FMD and rapamycin interventions on cognition relative to the placebo group.
NIH Toolbox Flanker and Pattern Comparison Tests and the Mayo Preclinical Alzheimer's Cognitive Composite.
The NIH Toolbox assessments are measured through scaled scores (T-scores), which range from 20-80 with higher scores indicating better outcomes. The Mayo Preclinical Alzheimer's Cognitive Composite is also measured using a standardized score (Z-score) with mean of 0 and a standard deviation of 1. Higher scores indicate better performance.
Measured: From pre- to post-treatment (Day 72 +/- 5 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Nov 2024
- Study startNov 2026 (estimated)
- Primary completionMar 2028 (estimated)
- Study completionJun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cerebral Blood FlowStudies of the same condition, open and under way.
- More trials run by Cedars-Sinai Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1/2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cedars-Sinai Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mitzi Gonzales, Cedars-Sinai Medical Center
- Investigators
- Mitzi Gonzales, PhD, Principal investigator, Cedars-Sinai Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06682767
- Sponsor's protocol ID
- STUDY00003359
- Status last verified
- Sep 2026
- First submitted
- 29 Oct 2024
- Last updated
- 16 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data collected for this study will be analyzed and stored at Cedars Sinai. After the study is completed, the de-identified, archived data will be stored at Cedars Sinai for use by other researchers including those outside of the study. As new relevant methodologies are developed, however, there is a conceivable future interest to process deidentified samples and data in a collaborating laboratory at Cedars-Sinai Medical Center or outside of Cedars-Sinai Medical Center including commercial entities. Participants are made aware of this possibility in the written informed consent form at the time of enrollment and are informed that to consent to this study is also to consent to permit coded data to be shared for the purposes of this research. The key to the code is not shared with collaborators but will remain in a HIPAA-compliant, secure, REDCap database at Cedars-Sinai Medical Center.
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Nutritional and Pharmacological Intervention for Body, Brain, and Longevity Effects (NIBBLE) - A Randomized Open-label Intervention of the Fasting-mimicking Diet (FMD) and Rapamycin (NIBBLE)
- ClinicalTrials.gov ID
- NCT06682767
- Acronym / sponsor ID
- STUDY00003359
- Conditions
- Cerebral Blood Flow, APOE 4
- Keywords
- APOE 4, prevention, nutritition, fasting mimicking diet, diet, Alzheimer's disease, rapamycin
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Cedars-Sinai Medical CenterUniversity, hospital or other
- Study start
- Nov 2026 (estimated)
- Primary completion
- Mar 2028 (estimated)
- Study completion
- Jun 2028 (estimated)
- First posted
- 12 Nov 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study aims to evaluate the safety, feasibility, and preliminary efficacy of the fasting-mimicking diet (FMD) or low-dose daily rapamycin treatment relative to a matched placebo control group when administered over 8 weeks in middle-aged adults at elevated risk for Alzheimer's disease due to the apolipoprotein (APOE) ε4 allele. Participants randomly assigned to the FMD intervention will adhere to FMD for 5-days over three cycles for a period of approximately 8 weeks. Participants randomly assigned to the rapamycin and placebo groups will take 1 mg of rapamycin or a matched placebo pill daily for approximately 8 weeks.
Detailed description
Participants assigned to the FMD arm will adhere to the diet for 5 days over three cycles for a period of 8 weeks. The FMD diet is produced by L-Nutra and provides 1100 kcals on day 1 and 800 kcals on days 2-5. The diet consists of ingredients which are Generally Regarded As Safe (GRAS) selected for their fasting mimicking properties. Participants randomized to the rapamycin group will receive 1 mg rapamycin daily for 8 weeks and those in the placebo arm will take one matched placebo pill daily for 8 weeks.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| FMD - Intervention | Experimental | Dietary Supplement: FMD1 (LNT22-017-1)Participants in the FMD group will be asked to refrain from consuming any calorie-containing foods or drinks other than the provided study foods/drinks during the designated intervention days each month. |
| Rapamycin | Experimental | Drug: RapamycinParticipants randomly assigned to the rapamycin arm will take 1 mg of rapamycin daily for approximately 8 weeks. |
| Placebo | Placebo comparator | Drug: PlaceboParticipants randomly assigned to the placebo arm will take one placebo pill daily for approximately 8 weeks. |
Who may qualify
- Ages
- 45 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Provision of signed and dated informed consent form
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Male or female, aged 45-65 years at screening
- Carrier of at least one copy of the APOE e4 allele
- BMI 20-39kg/m2 (inclusive) at screening
Key exclusion criteria (25 listed)
- Has any medical disease or condition that, in the opinion of the principal investigator (PI) or appropriate study personnel, precludes study participation* (*Including acute, subacute, intermittent or chronic medical disease or condition that would place the subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the subject's successful completion of this trial);
- Significant depression (PHQ-9>9) or generalized anxiety (GAD-7>9)
- Diagnosis of a significant neurological condition such as multiple sclerosis, epilepsy, Parkinson's disease, major stroke
- Contraindications to MRI such as claustrophobia, cardiac pacemaker, etc.
- Current adherence or adherence within the past 3 months to a specialized diet (e.g. ketogenic, paleo, intermittent fasting, raw food, vegan)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FMD1 (LNT22-017-1)FMD is a plant-based ketogenic diet that provides essential nutrients while maintaining hypo-caloric content. FMD is administered cyclically with 3-5 consecutive days of the diet followed by resumption of normal eating. | Dietary supplement | FMD - Intervention |
| RapamycinParticipants randomly assigned to the rapamycin arm will take 1 mg of rapamycin daily for approximately 8 weeks.. | Drug | Rapamycin |
| PlaceboParticipants randomly assigned to the placebo arm will take one placebo pill daily for approximately 8 weeks. | Drug | Placebo |
Primary outcome
Evaluate and compare the safety of an approximately 8-week FMD or low dose rapamycin intervention relative to a matched control group
Time frame: From pre- to post-treatment (Day 72 +/- 5 days)
Endpoint: Number of adverse events in the intervention groups relative to the placebo group.
2 secondary outcomes
Investigate the effect of an approximately 8-week FMD or low dose rapamycin intervention relative to a matched control group.
Time frame: From pre- to post-treatment (Day 72 +/- 5 days)
Investigate and compare the impact of the FMD and rapamycin interventions on cognition relative to the placebo group.
Time frame: From pre- to post-treatment (Day 72 +/- 5 days)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2026.
- Individual participant dataSharing planned: Yes. Data collected for this study will be analyzed and stored at Cedars Sinai. After the study is completed, the de-identified, archived data will be stored at Cedars Sinai for use by other researchers including those outside of the study. As new relevant methodologies are developed, however, there is a conceivable future interest to process deidentified samples and data in a collaborating laboratory at Cedars-Sinai Medical Center or outside of Cedars-Sinai Medical Center including commercial entities. Participants are made aware of this possibility in the written informed consent form at the time of enrollment and are informed that to consent to this study is also to consent to permit coded data to be shared for the purposes of this research. The key to the code is not shared with collaborators but will remain in a HIPAA-compliant, secure, REDCap database at Cedars-Sinai Medical Center.
Related trials for Cerebral Blood Flow
RecruitingObservational study
Studies of Blood Flow to the Brain During Thought
Healthy Volunteer
RecruitingObservational study
Association of Prophylactic Use of Stress Ulcer Drugs and Clinical Outcomes in Patients With Acute Anterior Circulation Thrombectomy
Acute Ischemic Stroke
Not yet recruitingObservational study
Multimodal MRI Assessment of Brain Fluid Circulation in Idiopathic Intracranial Hypertension
Idiopathic Intracranial Hypertension
Not yet recruitingObservational study
Heart and Brain Blood Flow in Obstructive Sleep Apnea
Obstructive Sleep Apnea (OSA)
Not yet recruitingObservational study
Brain-based Prediction of the Dying Duration in Humans After Withdrawal of Life Sustaining Therapies to Inform Donation After Circulatory Death
Organ Donation After Circulatory Death
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Mitzi Gonzales, PhD principal investigator
Cedars-Sinai Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing FMD1 (LNT22-017-1) and Rapamycin in people with Cerebral Blood Flow and APOE 4, run by Cedars-Sinai Medical Center at 1 site in United States.
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 7 inclusion and 25 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: opening soon, as of the sponsor's last update on 16 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 Mitzi Gonzales, PhD (424-315-0228, mitzi.gonzales@cshs.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluate and compare the safety of an approximately 8-week FMD or low dose rapamycin intervention relative to a matched control group (time frame: From pre- to post-treatment (Day 72 +/- 5 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 Sep 2026.