Type 1 HyperlipoproteinemiaPhase 2NCT01675154
Phase 2 Study of Orlistat and SLx-4090 for the Treatment of Type 1 Hyperlipoproteinemia
A Phase 2 study testing Orlistat and Slx-4090 in people with Type 1 Hyperlipoproteinemia, run by University of Texas Southwestern Medical Center at 2 sites in United States.
Trial summary
Funding Source - FDA OOPD This study is being done to find out whether an investigational (not approved by FDA ) drug called SLx-4090 or Orlistat (FDA approved medication for weight loss) when given alone or in combination can treat the high blood fat (elevated triglycerides)levels found in the condition Type 1… Read more about this study
- Who is it for?
- Ages 12 to 100 years
- Conditions the study is for
- Type 1 Hyperlipoproteinemia
- What is being tested?
- Orlistat and Slx-4090
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 5 participants
- Where
- 2 sitesUnited States
- Study dates
- Nov 2015to 30 Jun 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 12 to 100 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Type I hyperlipoproteinemia.
- Fasting serum triglyceride levels of greater than 1000 mg/dL.
- Age > 12 years
Who cannot join
- Secondary hypertriglyceridemias due to diabetes, renal disease, hypothyroidism, alcoholism and drug therapy such as estrogens and estrogen analogues, steroids, HIV-protease inhibitors, retinoic acid derivatives and interferons.
- Pregnant or lactating women
- Significant liver disease (elevated transaminases > 2 times upper limit of normal)
- Alcohol abuse (> 7 drinks or 84 g per week for women and > 14 drinks for men or 168 g per week for men)
- Drug use (cocaine, marijuana, LSD, etc.)
- Major surgery in the past three months
Show all 14Show fewer
- Congestive heart failure
- Serum creatinine greater than 2.5 mg/dL
- Cancer within the past five years
- Gastrointestinal surgery in the past
- Current therapy with anti-coagulants, digoxin and anti-arrhythmics
- Chronic malabsorption syndromes
- Cholestasis
- Acute illnesses such as acute pancreatitis in the last 8 weeks
Trial locations and contacts
2 sites in 1 country.
United States2 sites
UT Southwestern Medical Center 5323 Harry Hines Blvd
Dallas, Texas, 75390-8537
UT Southwestern Medical Center
Dallas, Texas, 75390
About this study
Funding Source - FDA OOPD
This study is being done to find out whether an investigational (not approved by FDA ) drug called SLx-4090 or Orlistat (FDA approved medication for weight loss) when given alone or in combination can treat the high blood fat (elevated triglycerides)levels found in the condition Type 1 Hyperlipoproteinemia (T1HLP) better or more safely than low fat diet alone, the current standard medical care.
It is also not clear whether Orlistat, that is FDA approved for weight loss, is effective in lowering blood fat levels in patients with Type 1 hyperlipoproteinemia (T1HLP). The researchers are interested in learning whether any one of these drugs when given alone or in combination is more effective and safe in treating T1HLP.
Read the detailed description
Type I hyperlipoproteinemia is a rare, autosomal recessive metabolic disorder characterized by extreme hypertriglyceridemia due to a deficiency in lipoprotein lipase or related proteins. Treatment of these patients is challenging as triglyceride-lowering medications are ineffective. A low fat diet is helpful, however, despite good dietary compliance, some patients continue to have severe hypertriglyceridemia and recurrent pancreatitis which can be life threatening. Therefore, we wish to investigate whether inducing dietary fat malabsorption or inhibiting chylomicron formation will cause further lowering of serum triglycerides (TG) beyond the effect of limiting dietary fat intake.
We will study the efficacy and safety of an inhibitor of intestinal lipase (Orlistat) and an intestinal-specific inhibitor of microsomal triglyceride transport protein (MTP) involved in the assembly and secretion of chylomicrons (SLx-4090), alone and in combination, for reducing serum triglyceride levels in patients with Type I hyperlipoproteinemia. We plan to enroll 20 patients with Type I hyperlipoproteinemia in a randomized, double-blind, placebo-controlled, cross-over trial. After a baseline evaluation, the subjects will be randomly assigned to placebo/placebo, Orlistat/placebo, SLx-4090/placebo or Orlistat/SLx-4090 for the duration of four weeks followed by a one week wash out period. During the last week of each study period, fasting blood samples will be drawn for three consecutive days for serum lipids and chemistry panel. The primary endpoint will be serum triglycerides; the secondary endpoint variables will be fasting and postprandial serum chylomicron-TG levels, postprandial serum TG levels during a meal tolerance test and retinyl palmitate levels during a meal tolerance test. Repeated measures analysis of variance will be used for statistical comparisons.
Our results may help in designing novel therapeutic approaches for patients with Type 1 hyperlipoproteinemia.
- Conditions
- Type 1 Hyperlipoproteinemia
- Being tested
- SLx-4090 placebo, Orlistat Placebo, Orlistat, Slx-4090
- Keywords
- hypertriglyceridemia
- Medical subject headings
- Familial hyperchylomicronemia syndrome, Hypertriglyceridemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SLx-4090 placeboDrug
Given for 4 weeks
Orlistat PlaceboDrug
Given for 4 weeks
OrlistatDrug
Given for 4 weeks
Slx-4090Drug
Given for 4 weeks
| Study group | Role | What they receive |
|---|---|---|
| SLx-4090 placebo/Orlistat Placebo | Placebo comparator | Slx-4090(placebo) is dosed as 4 tablets of 50 mg, three times per day with meals.
Orlistat (placebo) is dosed as 2 capsules of 60 mg, three times per day with meals.
This trial is adaptive design/flexible design. The participants were either randomized from the start of the study or after the completion of each treatment. Receives: Drug: SLx-4090 placebo; Drug: Orlistat Placebo |
| Orlistat/placebo | Experimental | Orlistat two capsules 60mg each, three times per day with meals. Placebo for SLx-4090, 4 tablets 50mg each, three times per day with meals. This trial is adaptive design/flexible design. The participants were either randomized from the start of the study or after the completion of each treatment. Receives: Drug: SLx-4090 placebo; Drug: Orlistat |
| Orlistat placebo /SLx-4090 | Experimental | Orlistat placebo 2 capsules, 60mg each three times per day with meals. Slx-4090 4 tablets, 50mg each. three times per day with meals. This trial is adaptive design/flexible design. The participants were either randomized from the start of the study or after the completion of each treatment. Receives: Drug: Orlistat Placebo; Drug: Slx-4090 |
| Orlistat/SLx-4090 | Experimental | Orlistat, 2 capsules 60 mg each, three times per day with meals. SLx-4090 4 tablets 50mg each, three times per day with meals. This trial is adaptive design/flexible design. The participants were either randomized from the start of the study or after the completion of each treatment. Receives: Drug: Orlistat; Drug: Slx-4090 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum Triglycerides at First Intervention Period
Serum triglyceride level will be measured after taking each assigned intervention at first intervention period.
Measured: 4 weeks after the assigned treatment (first intervention period)
Serum Triglycerides at Second Intervention Period
Serum triglyceride level will be measured after taking each assigned intervention at second intervention period
Measured: 4 weeks after the assigned treatment (Second Intervention Period)
Serum Triglycerides at Third Intervention Period
Serum triglyceride level will be measured after taking each assigned intervention at intervention period
Measured: 4 weeks after the assigned treatment (Third Intervention Period)
Serum Triglycerides at Fourth Intervention Period
Serum triglyceride level will be measured after taking each assigned intervention at fourth intervention period
Measured: 4 weeks after the assigned treatment (Fourth Intervention Period)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2012 (estimated)
- Study startNov 2015
- Primary completion30 Jun 2020
- Study completion30 Jun 2020
Why it stopped: Due to unavailability of the drug.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Type 1 HyperlipoproteinemiaStudies of the same condition, open and under way.
- More trials run by University of Texas Southwestern 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- This trial is adaptive design/flexible design. The participants were randomized from the start of the study
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Abhimanyu Garg, University of Texas Southwestern Medical Center
- Investigators
- Abhimanyu Garg, MD, Principal investigator, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01675154
- Sponsor's protocol ID
- 3940
- Other IDs
- FD-R-003940
- Status last verified
- Jul 2021
- First submitted
- 27 Aug 2012
- Last updated
- 19 Aug 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Study of Orlistat and SLx-4090 for the Treatment of Type 1 Hyperlipoproteinemia
- ClinicalTrials.gov ID
- NCT01675154
- Acronym / sponsor ID
- 3940
- Conditions
- Type 1 Hyperlipoproteinemia
- Keywords
- hypertriglyceridemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to unavailability of the drug.
- Enrolment
- 5 participants (actual)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Study start
- Nov 2015 (actual)
- Primary completion
- 30 Jun 2020 (actual)
- Study completion
- 30 Jun 2020 (actual)
- First posted
- 29 Aug 2012 (estimated)
- Results
- Posted 19 Aug 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Funding Source - FDA OOPD
This study is being done to find out whether an investigational (not approved by FDA ) drug called SLx-4090 or Orlistat (FDA approved medication for weight loss) when given alone or in combination can treat the high blood fat (elevated triglycerides)levels found in the condition Type 1 Hyperlipoproteinemia (T1HLP) better or more safely than low fat diet alone, the current standard medical care.
It is also not clear whether Orlistat, that is FDA approved for weight loss, is effective in lowering blood fat levels in patients with Type 1 hyperlipoproteinemia (T1HLP). The researchers are interested in learning whether any one of these drugs when given alone or in combination is more effective and safe in treating T1HLP.
Detailed description
Type I hyperlipoproteinemia is a rare, autosomal recessive metabolic disorder characterized by extreme hypertriglyceridemia due to a deficiency in lipoprotein lipase or related proteins. Treatment of these patients is challenging as triglyceride-lowering medications are ineffective. A low fat diet is helpful, however, despite good dietary compliance, some patients continue to have severe hypertriglyceridemia and recurrent pancreatitis which can be life threatening. Therefore, we wish to investigate whether inducing dietary fat malabsorption or inhibiting chylomicron formation will cause further lowering of serum triglycerides (TG) beyond the effect of limiting dietary fat intake.
We will study the efficacy and safety of an inhibitor of intestinal lipase (Orlistat) and an intestinal-specific inhibitor of microsomal triglyceride transport protein (MTP) involved in the assembly and secretion of chylomicrons (SLx-4090), alone and in combination, for reducing serum triglyceride levels in patients with Type I hyperlipoproteinemia. We plan to enroll 20 patients with Type I hyperlipoproteinemia in a randomized, double-blind, placebo-controlled, cross-over trial. After a baseline evaluation, the subjects will be randomly assigned to placebo/placebo, Orlistat/placebo, SLx-4090/placebo or Orlistat/SLx-4090 for the duration of four weeks followed by a one week wash out period. During the last week of each study period, fasting blood samples will be drawn for three consecutive days for serum lipids and chemistry panel. The primary endpoint will be serum triglycerides; the secondary endpoint variables will be fasting and postprandial serum chylomicron-TG levels, postprandial serum TG levels during a meal tolerance test and retinyl palmitate levels during a meal tolerance test. Repeated measures analysis of variance will be used for statistical comparisons.
Our results may help in designing novel therapeutic approaches for patients with Type 1 hyperlipoproteinemia.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- This trial is adaptive design/flexible design. The participants were randomized from the start of the study
| Arm | Type | Receives |
|---|---|---|
| SLx-4090 placebo/Orlistat Placebo | Placebo comparator | Drug: SLx-4090 placebo, Drug: Orlistat PlaceboSlx-4090(placebo) is dosed as 4 tablets of 50 mg, three times per day with meals. Orlistat (placebo) is dosed as 2 capsules of 60 mg, three times per day with meals. This trial is adaptive design/flexible design. The participants were either randomized from the start of the study or after the completion of each treatment. |
| Orlistat/placebo | Experimental | Drug: SLx-4090 placebo, Drug: OrlistatOrlistat two capsules 60mg each, three times per day with meals. Placebo for SLx-4090, 4 tablets 50mg each, three times per day with meals. This trial is adaptive design/flexible design. The participants were either randomized from the start of the study or after the completion of each treatment. |
| Orlistat placebo /SLx-4090 | Experimental | Drug: Orlistat Placebo, Drug: Slx-4090Orlistat placebo 2 capsules, 60mg each three times per day with meals. Slx-4090 4 tablets, 50mg each. three times per day with meals. This trial is adaptive design/flexible design. The participants were either randomized from the start of the study or after the completion of each treatment. |
| Orlistat/SLx-4090 | Experimental | Drug: Orlistat, Drug: Slx-4090Orlistat, 2 capsules 60 mg each, three times per day with meals. SLx-4090 4 tablets 50mg each, three times per day with meals. This trial is adaptive design/flexible design. The participants were either randomized from the start of the study or after the completion of each treatment. |
Who may qualify
- Ages
- 12 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Type I hyperlipoproteinemia.
- Fasting serum triglyceride levels of greater than 1000 mg/dL.
- Age > 12 years
Key exclusion criteria (14 listed)
- Secondary hypertriglyceridemias due to diabetes, renal disease, hypothyroidism, alcoholism and drug therapy such as estrogens and estrogen analogues, steroids, HIV-protease inhibitors, retinoic acid derivatives and interferons.
- Pregnant or lactating women
- Significant liver disease (elevated transaminases > 2 times upper limit of normal)
- Alcohol abuse (> 7 drinks or 84 g per week for women and > 14 drinks for men or 168 g per week for men)
- Drug use (cocaine, marijuana, LSD, etc.)
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 |
|---|---|---|
| SLx-4090 placeboGiven for 4 weeks | Drug | Orlistat/placebo, SLx-4090 placebo/Orlistat Placebo |
| Orlistat PlaceboGiven for 4 weeks | Drug | Orlistat placebo /SLx-4090, SLx-4090 placebo/Orlistat Placebo |
| OrlistatGiven for 4 weeks | Drug | Orlistat/SLx-4090, Orlistat/placebo |
| Slx-4090Given for 4 weeks | Drug | Orlistat placebo /SLx-4090, Orlistat/SLx-4090 |
Primary outcome
Serum Triglycerides at First Intervention Period
Time frame: 4 weeks after the assigned treatment (first intervention period)
Serum triglyceride level will be measured after taking each assigned intervention at first intervention period.
Serum Triglycerides at Second Intervention Period
Time frame: 4 weeks after the assigned treatment (Second Intervention Period)
Serum triglyceride level will be measured after taking each assigned intervention at second intervention period
Serum Triglycerides at Third Intervention Period
Time frame: 4 weeks after the assigned treatment (Third Intervention Period)
Serum triglyceride level will be measured after taking each assigned intervention at intervention period
Serum Triglycerides at Fourth Intervention Period
Time frame: 4 weeks after the assigned treatment (Fourth Intervention Period)
Serum triglyceride level will be measured after taking each assigned intervention at fourth intervention period
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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. This study is not recruiting at the moment.
Abhimanyu Garg, MD principal investigator
University of Texas Southwestern Medical Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Orlistat and Slx-4090 in people with Type 1 Hyperlipoproteinemia, run by University of Texas Southwestern Medical Center at 2 sites 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 3 inclusion and 14 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: stopped early, as of the sponsor's last update on 19 Aug 2021. 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 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 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?
Yes. Results are posted in the registry (first posted 19 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Serum Triglycerides at First Intervention Period (time frame: 4 weeks after the assigned treatment (first intervention period)). The study lists 4 primary outcomes in all. 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 19 Aug 2021.